RGD DISEASE ONTOLOGY - ANNOTATIONS
RGD uses the Human Disease Ontology (DO, https://disease-ontology.org/) for disease curation across species. RGD automatically downloads each new release of the ontology on a monthly basis. Some additional terms which are required for RGD's curation purposes but are not currently covered in the official version of DO have been added. As corresponding terms are added to DO, these custom terms are retired and the DO terms substituted in existing annotations and subsequently used for curation.
Term: holoprosencephaly
Accession: DOID:4621
browse the term
Definition: Anterior midline brain, cranial, and facial malformations resulting from the failure of the embryonic prosencephalon to undergo segmentation and cleavage. Alobar prosencephaly is the most severe form and features anophthalmia; cyclopia; severe INTELLECTUAL DISABILITY; CLEFT LIP; CLEFT PALATE; SEIZURES; and microcephaly. Semilobar holoprosencepaly is characterized by hypotelorism, microphthalmia, coloboma, nasal malformations, and variable degrees of INTELLECTUAL DISABILITY. Lobar holoprosencephaly is associated with mild (or absent) facial malformations and intellectual abilities that range from mild INTELLECTUAL DISABILITY to normal. Holoprosencephaly is associated with CHROMOSOME ABNORMALITIES.
Synonyms: exact_synonym: Arhinencephaly; DeMyer sequence; HPE, FAMILIAL; HPEC; Holoprosencephalies; Holoprosencephaly sequence; Holoprosencephaly, Familial Alobar; alobar holoprosencephalies; alobar holoprosencephaly; arhinencephalies; lobar holoprosencephalies; lobar holoprosencephaly; semilobar holoprosencephalies; semilobar holoprosencephaly
narrow_synonym: microform holoprosencephaly
primary_id: MESH:D016142
xref: GARD:6665 ; ICD10CM:Q04.2 ; NCI:C74988 ; OMIM:PS236100 ; ORDO:2162
For additional species annotation, visit the
Alliance of Genome Resources .
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Boc
BOC cell adhesion associated, oncogene regulated
ISO
ClinVar Annotator: match by term: Holoprosencephaly
ClinVar
PMID:28677295
NCBI chr11:61,084,216...61,159,220
Ensembl chr11:61,083,757...61,158,838
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Cdon
cell adhesion associated, oncogene regulated
ISO
ClinVar Annotator: match by term: Holoprosencephaly
ClinVar
NCBI chr 8:36,625,757...36,712,091
Ensembl chr 8:36,625,733...36,710,949
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Cnot1
CCR4-NOT transcription complex, subunit 1
ISO
ClinVar Annotator: match by term: Holoprosencephaly sequence
ClinVar
PMID:25741868 PMID:28525974 PMID:31006510 PMID:31006513 PMID:32553196
NCBI chr19:9,668,186...9,761,605
Ensembl chr19:9,668,186...9,761,605
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Creb1
cAMP responsive element binding protein 1
ISO
protein:increased localization: prechordal mesoderm, nucleus
RGD
PMID:18338389
RGD:12801437
NCBI chr 9:71,229,753...71,298,994
Ensembl chr 9:71,230,108...71,293,435
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Disp1
dispatched RND transporter family member 1
ISO
ClinVar Annotator: match by term: Lobar holoprosencephaly ClinVar Annotator: match by term: Holoprosencephaly
ClinVar
PMID:25741868
NCBI chr13:101,451,932...101,597,570
Ensembl chr13:101,451,932...101,597,570
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Dll1
delta like canonical Notch ligand 1
ISO
ClinVar Annotator: match by term: Holoprosencephaly ClinVar Annotator: match by term: Holoprosencephaly sequence
ClinVar
PMID:28492532
NCBI chr 1:57,318,621...57,326,732
Ensembl chr 1:57,318,708...57,327,379
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Fgf8
fibroblast growth factor 8
ISO
ClinVar Annotator: match by term: Semilobar holoprosencephaly ClinVar Annotator: match by term: Holoprosencephaly sequence
ClinVar
PMID:20463092 PMID:22399515 PMID:25131394 PMID:25741868 PMID:26467025 PMID:26857713 PMID:26931467 PMID:28492532 PMID:29584859
NCBI chr 1:265,492,949...265,498,965
Ensembl chr 1:265,493,124...265,498,831
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Fgfr1
Fibroblast growth factor receptor 1
ISO
ClinVar Annotator: match by term: Semilobar holoprosencephaly ClinVar Annotator: match by term: Holoprosencephaly
ClinVar
PMID:26931467
NCBI chr16:71,265,390...71,319,046
Ensembl chr16:71,266,248...71,319,449
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Foxh1
forkhead box H1
ISO
ClinVar Annotator: match by term: Holoprosencephaly ClinVar Annotator: match by term: Holoprosencephaly sequence
ClinVar
PMID:18538293 PMID:25741868 PMID:28492532
NCBI chr 7:117,730,307...117,733,076
Ensembl chr 7:117,730,307...117,732,387
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Fras1
Fraser extracellular matrix complex subunit 1
ISO
ClinVar Annotator: match by term: Alobar holoprosencephaly
ClinVar
PMID:30311386
NCBI chr14:14,438,392...14,853,016
Ensembl chr14:14,439,082...14,689,554
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Frem2
FRAS1 related extracellular matrix 2
ISO
ClinVar Annotator: match by term: Alobar holoprosencephaly
ClinVar
PMID:30311386
NCBI chr 2:142,747,501...142,885,604
Ensembl chr 2:142,747,501...142,885,604
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Gas1
growth arrest-specific 1
ISO
CTD Direct Evidence: marker/mechanism
CTD
PMID:17525797
NCBI chr17:4,846,116...4,849,350
Ensembl chr17:4,846,789...4,847,940
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Gli2
GLI family zinc finger 2
ISO
ClinVar Annotator: match by term: microform holoprosencephaly CTD Direct Evidence: marker/mechanism
ClinVar CTD
PMID:27585885
NCBI chr13:34,829,021...35,049,172
Ensembl chr13:34,829,139...35,048,444
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Kifc2
kinesin family member C2
ISO
ClinVar Annotator: match by term: Holoprosencephaly
ClinVar
NCBI chr 7:117,722,732...117,730,702
Ensembl chr 7:117,723,263...117,730,702
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Lama5
laminin subunit alpha 5
ISO
ClinVar Annotator: match by term: Holoprosencephaly sequence
ClinVar
PMID:25741868 PMID:28735299 PMID:29534211 PMID:31680349
NCBI chr 3:175,553,042...175,601,112
Ensembl chr 3:175,553,045...175,601,127
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Matn4
matrilin 4
ISO
ClinVar Annotator: match by term: DEMYER SEQUENCE
ClinVar
PMID:25558065
NCBI chr 3:160,838,632...160,853,650
Ensembl chr 3:160,838,632...160,853,650
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Nodal
nodal growth differentiation factor
ISO
CTD Direct Evidence: marker/mechanism ClinVar Annotator: match by term: Holoprosencephaly sequence
CTD ClinVar
PMID:19064609 PMID:19553149 PMID:22352765 PMID:23264560 PMID:24033266 PMID:25741868 PMID:28492532
NCBI chr20:31,035,729...31,044,096
Ensembl chr20:31,035,729...31,044,096
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Pgap1
post-GPI attachment to proteins inositol deacylase 1
ISS
MouseDO
NCBI chr 9:61,066,170...61,134,963
Ensembl chr 9:61,066,175...61,134,963
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Pign
phosphatidylinositol glycan anchor biosynthesis, class N
ISS
MouseDO
NCBI chr13:25,510,593...25,662,943
Ensembl chr13:25,513,892...25,652,473
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Ptch1
patched 1
ISO
ClinVar Annotator: match by term: Holoprosencephaly ClinVar Annotator: match by term: Holoprosencephaly sequence DNA:missense mutations:exon:multiple
ClinVar
PMID:8302318 PMID:11941477 PMID:17001668 PMID:21188540 PMID:22703879 PMID:22820256 PMID:24055113 PMID:24728327 PMID:25637381 PMID:26489027 PMID:26893459 PMID:27153395 PMID:28492532 , PMID:11941477
RGD:12798567
NCBI chr17:1,032,242...1,085,885
Ensembl chr17:1,029,048...1,093,873
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Shh
sonic hedgehog signaling molecule
treatment
ISO
DNA:mutations:cds:multiple (human) ClinVar Annotator: match by term: Alobar holoprosencephaly CTD Direct Evidence: marker/mechanism ClinVar Annotator: match by term: Holoprosencephaly DNA:missense mutation:CDS:p.V88D (263A>T) (human) DNA:missense mutations, non-sense mutation:exon:multiple
ClinVar CTD
PMID:15107988 PMID:17525797 PMID:23264560 PMID:27585885 PMID:29584859 PMID:30311386 PMID:31642701 , PMID:8896572 , PMID:18338389 , PMID:11919111 , PMID:10441331
RGD:9743971 , RGD:12801437 , RGD:12801425 , RGD:12798570
NCBI chr 4:718,538...727,691
Ensembl chr 4:718,538...727,691
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Six3
SIX homeobox 3
ISO
CTD Direct Evidence: marker/mechanism
CTD
PMID:10369266 , PMID:10369266 , PMID:15523651
RGD:1599336 , RGD:1599335
NCBI chr 6:8,886,730...8,891,094
Ensembl chr 6:8,886,591...8,889,925
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Sufu
SUFU negative regulator of hedgehog signaling
ISO
ClinVar Annotator: match by term: microform holoprosencephaly
ClinVar
PMID:24728327 PMID:27363716 PMID:28492532
NCBI chr 1:266,143,766...266,241,742
Ensembl chr 1:266,143,818...266,239,016
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Tdgf1
teratocarcinoma-derived growth factor 1
ISO
CTD Direct Evidence: marker/mechanism
CTD
PMID:12073012
NCBI chr 8:119,215,266...119,220,909
Ensembl chr 8:119,215,495...119,219,232
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Tgif1
TGFB-induced factor homeobox 1
ISO
holoprosencephaly-4, OMIM:142946 ClinVar Annotator: match by term: Holoprosencephaly CTD Direct Evidence: marker/mechanism
ClinVar CTD
PMID:16705179 PMID:25741868 PMID:28492532 , PMID:10835638
RGD:1599407
NCBI chr 9:119,181,079...119,190,698
Ensembl chr 9:119,181,083...119,190,698
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Twsg1
twisted gastrulation BMP signaling modulator 1
ISO
CTD Direct Evidence: marker/mechanism
CTD
PMID:15013800
NCBI chr 9:113,699,151...113,732,601
Ensembl chr 9:113,699,170...113,732,622
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Zic2
Zic family member 2
ISO
ClinVar Annotator: match by term: Holoprosencephaly sequence DNA:insertion,deletion mutations:cds: DNA:deletion, duplication, frameshift, transition mutations:cds,intron:
ClinVar
PMID:25741868 , PMID:18617531 , PMID:9771712 , PMID:22847929
RGD:11561948 , RGD:11561954 , RGD:11561949
NCBI chr15:108,908,366...108,913,812
Ensembl chr15:108,908,607...108,912,737
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Zrsr2
zinc finger (CCCH type), RNA binding motif and serine/arginine rich 2
ISO
ClinVar Annotator: match by term: Holoprosencephaly sequence
ClinVar
PMID:25679214 PMID:25741868 PMID:31680349
NCBI chr X:32,304,707...32,327,419
Ensembl chr X:32,304,757...32,328,364
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Foxh1
forkhead box H1
ISS
OMIM:202650
MouseDO
NCBI chr 7:117,730,307...117,733,076
Ensembl chr 7:117,730,307...117,732,387
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Prrx1
paired related homeobox 1
ISO
ClinVar Annotator: match by term: Agnathia-otocephaly complex ClinVar Annotator: match by term: Dysgnathia complex CTD Direct Evidence: marker/mechanism ClinVar Annotator: match by OMIM:202650
OMIM ClinVar CTD
PMID:12244557 PMID:21294718 PMID:22211708 PMID:22674740 PMID:23444262 PMID:25741868
NCBI chr13:81,147,038...81,215,559
Ensembl chr13:81,147,348...81,214,546
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Trappc10
trafficking protein particle complex 10
ISS
OMIM:202650
MouseDO
NCBI chr20:11,168,298...11,228,634
Ensembl chr20:11,168,298...11,228,625
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Cdon
cell adhesion associated, oncogene regulated
ISO
ClinVar Annotator: match by term: Holoprosencephaly 1
ClinVar
PMID:25741868
NCBI chr 8:36,625,757...36,712,091
Ensembl chr 8:36,625,733...36,710,949
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Fgf8
fibroblast growth factor 8
ISO
ClinVar Annotator: match by term: Holoprosencephaly 1
ClinVar
PMID:18596921 PMID:21045958
NCBI chr 1:265,492,949...265,498,965
Ensembl chr 1:265,493,124...265,498,831
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Gas1
growth arrest-specific 1
ISO
ClinVar Annotator: match by term: Holoprosencephaly 1
ClinVar
PMID:20583177 PMID:21842183
NCBI chr17:4,846,116...4,849,350
Ensembl chr17:4,846,789...4,847,940
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Gli2
GLI family zinc finger 2
ISO
ClinVar Annotator: match by term: Holoprosencephaly 1
ClinVar
PMID:25741868
NCBI chr13:34,829,021...35,049,172
Ensembl chr13:34,829,139...35,048,444
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Zic2
Zic family member 2
ISO
ClinVar Annotator: match by term: Holoprosencephaly 1
ClinVar
PMID:22859937
NCBI chr15:108,908,366...108,913,812
Ensembl chr15:108,908,607...108,912,737
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Cdon
cell adhesion associated, oncogene regulated
ISO
ClinVar Annotator: match by term: Holoprosencephaly 11 ClinVar Annotator: match by OMIM:614226
OMIM ClinVar
PMID:21802063 PMID:25741868 PMID:28492532
NCBI chr 8:36,625,757...36,712,091
Ensembl chr 8:36,625,733...36,710,949
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Cnot1
CCR4-NOT transcription complex, subunit 1
ISO
ClinVar Annotator: match by term: HOLOPROSENCEPHALY 12 WITH OR WITHOUT PANCREATIC AGENESIS
OMIM ClinVar
PMID:25741868 PMID:28525974 PMID:31006510 PMID:31006513 PMID:32553196
NCBI chr19:9,668,186...9,761,605
Ensembl chr19:9,668,186...9,761,605
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Stag2
stromal antigen 2
ISO
ClinVar Annotator: match by term: HOLOPROSENCEPHALY 13, X-LINKED
OMIM ClinVar
PMID:28296084 PMID:30765867 PMID:31334757
NCBI chr X:128,493,603...128,624,418
Ensembl chr X:128,493,614...128,624,418
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Six3
SIX homeobox 3
ISO
ClinVar Annotator: match by term: Holoprosencephaly 2 ClinVar Annotator: match by OMIM:157170
OMIM ClinVar
PMID:10369266 PMID:10923031 PMID:11039582 PMID:15221788 PMID:15523651 PMID:17001667 PMID:17584896 PMID:18791198 PMID:19346217 PMID:19353631 PMID:20157829 PMID:20531442 PMID:25741868 PMID:26080100 PMID:26467025 PMID:28492532
NCBI chr 6:8,886,730...8,891,094
Ensembl chr 6:8,886,591...8,889,925
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Lmbr1
limb development membrane protein 1
ISO
ClinVar Annotator: match by term: Holoprosencephaly 3
ClinVar
PMID:28492532
NCBI chr 4:2,116,094...2,274,111
Ensembl chr 4:2,116,094...2,201,749
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Shh
sonic hedgehog signaling molecule
ISO
ClinVar Annotator: match by term: Holoprosencephaly 3 ClinVar Annotator: match by OMIM:142945
OMIM ClinVar
PMID:8896572 PMID:9302262 PMID:9600232 PMID:10479723 PMID:10556296 PMID:11471164 PMID:11857543 PMID:11919111 PMID:12567406 PMID:12709790 PMID:15292211 PMID:16282375 PMID:18655123 PMID:19478089 PMID:19533790 PMID:19603532 PMID:19920144 PMID:20157829 PMID:20425842 PMID:21416594 PMID:22897141 PMID:25741868 PMID:26467025 PMID:28127823 PMID:28492532 PMID:29205322 PMID:30311386
NCBI chr 4:718,538...727,691
Ensembl chr 4:718,538...727,691
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Tgif1
TGFB-induced factor homeobox 1
ISO
ClinVar Annotator: match by OMIM:142946 ClinVar Annotator: match by term: Holoprosencephaly 4
ClinVar OMIM
PMID:10835638 PMID:11810641 PMID:12522553 PMID:16199538 PMID:16962354 PMID:17001671 PMID:19431187 PMID:21940735 PMID:22125506 PMID:24123366 PMID:25741868 PMID:28492532
NCBI chr 9:119,181,079...119,190,698
Ensembl chr 9:119,181,083...119,190,698
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Clybl
citramalyl-CoA lyase
ISO
ClinVar Annotator: match by term: Holoprosencephaly 5
ClinVar
PMID:19955556 PMID:28492532
NCBI chr15:108,608,203...108,838,222
Ensembl chr15:108,608,204...108,838,235
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Tm9sf2
transmembrane 9 superfamily member 2
ISO
ClinVar Annotator: match by term: Holoprosencephaly 5
ClinVar
PMID:19955556 PMID:28492532
NCBI chr15:108,526,341...108,579,268
Ensembl chr15:108,526,014...108,579,256
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Ubac2
UBA domain containing 2
ISO
ClinVar Annotator: match by term: Holoprosencephaly 5
ClinVar
PMID:19955556 PMID:28492532
NCBI chr15:108,286,407...108,433,531
Ensembl chr15:108,286,453...108,433,529
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Zic2
Zic family member 2
ISO
ClinVar Annotator: match by term: Holoprosencephaly 5 ClinVar Annotator: match by OMIM:609637 ClinVar Annotator: match by null
OMIM ClinVar
PMID:9771712 PMID:11285244 PMID:11479728 PMID:15590697 PMID:19177455 PMID:19955556 PMID:21638761 PMID:21990207 PMID:22847929 PMID:25741868 PMID:28492532
NCBI chr15:108,908,366...108,913,812
Ensembl chr15:108,908,607...108,912,737
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Zic5
Zic family member 5
ISO
ClinVar Annotator: match by term: Holoprosencephaly 5
ClinVar
PMID:19955556 PMID:28492532
NCBI chr15:108,891,992...108,907,601
Ensembl chr15:108,891,992...108,898,703
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Ptch1
patched 1
ISO
ClinVar Annotator: match by term: Holoprosencephaly 7 ClinVar Annotator: match by OMIM:610828
OMIM ClinVar
PMID:1347096 PMID:8302318 PMID:9463336 PMID:11941477 PMID:12204003 PMID:12925203 PMID:15712338 PMID:16231297 PMID:16301862 PMID:17001668 PMID:17096318 PMID:17985375 PMID:18502968 PMID:19346217 PMID:20485063 PMID:21188540 PMID:21520333 PMID:22313357 PMID:22675565 PMID:22703879 PMID:22820256 PMID:22995991 PMID:23313819 PMID:23334667 PMID:23761049 PMID:23951062 PMID:24033266 PMID:24055113 PMID:24204797 PMID:24368541 PMID:24728327 PMID:24942795 PMID:25260786 PMID:25637381 PMID:25741868 PMID:26489027 PMID:26544948 PMID:26893459 PMID:27153395 PMID:27535533 PMID:27561271 PMID:27930734 PMID:28492532 PMID:28873162 PMID:29575684
NCBI chr17:1,032,242...1,085,885
Ensembl chr17:1,029,048...1,093,873
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Gli2
GLI family zinc finger 2
ISO
ClinVar Annotator: match by term: Holoprosencephaly 9 ClinVar Annotator: match by OMIM:610829
OMIM ClinVar
PMID:1756909 PMID:14581620 PMID:15994174 PMID:16327884 PMID:17096318 PMID:17569090 PMID:19223936 PMID:20685056 PMID:20685856 PMID:21204792 PMID:21416594 PMID:22967285 PMID:22978696 PMID:23408573 PMID:24744436 PMID:25741868 PMID:26893459 PMID:28492532 PMID:29876959 PMID:30311386 PMID:30548673
NCBI chr13:34,829,021...35,049,172
Ensembl chr13:34,829,139...35,048,444
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Fgfr1
Fibroblast growth factor receptor 1
ISO
ClinVar Annotator: match by null ClinVar Annotator: match by term: Hartsfield syndrome
ClinVar OMIM
PMID:15605412 PMID:16764984 PMID:19504604 PMID:23657145 PMID:23812909 PMID:24204987 PMID:24888332 PMID:25064402 PMID:25326635 PMID:25741868 PMID:26931467 PMID:28492532 PMID:31474318
NCBI chr16:71,265,390...71,319,046
Ensembl chr16:71,266,248...71,319,449
Term paths to the root one shortest all shortest one longest all longest one shortest and longest all
Path 1
disease
16085
syndrome
7041
holoprosencephaly
36
Genoa Syndrome
0
Holoprosencephaly 10
0
Holoprosencephaly 12
1
Holoprosencephaly 13
1
Holoprosencephaly with Fetal Akinesia/Hypokinesia Sequence
0
Holoprosencephaly, Ectrodactyly, and Bilateral Cleft Lip/Palate
1
Holoprosencephaly, Recurrent Infections, and Monocytosis
0
Lambotte Syndrome
0
Microgastria Limb Reduction Defect
0
Nonsyndromic Holoprosencephaly
0
Pseudotrisomy 13 Syndrome
0
Steinfeld Syndrome
0
agnathia-otocephaly complex
3
holoprosencephaly 1
5
holoprosencephaly 11
1
holoprosencephaly 2
1
holoprosencephaly 3
2
holoprosencephaly 4
1
holoprosencephaly 5
5
holoprosencephaly 6
0
holoprosencephaly 7
1
holoprosencephaly 8
0
holoprosencephaly 9
1
Path 2
disease
16085
Developmental Diseases
9586
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
8437
Congenital Abnormalities
4795
Nervous System Malformations
1102
Agenesis of Corpus Callosum
143
holoprosencephaly
36
Genoa Syndrome
0
Holoprosencephaly 10
0
Holoprosencephaly 12
1
Holoprosencephaly 13
1
Holoprosencephaly with Fetal Akinesia/Hypokinesia Sequence
0
Holoprosencephaly, Ectrodactyly, and Bilateral Cleft Lip/Palate
1
Holoprosencephaly, Recurrent Infections, and Monocytosis
0
Lambotte Syndrome
0
Microgastria Limb Reduction Defect
0
Nonsyndromic Holoprosencephaly
0
Pseudotrisomy 13 Syndrome
0
Steinfeld Syndrome
0
agnathia-otocephaly complex
3
holoprosencephaly 1
5
holoprosencephaly 11
1
holoprosencephaly 2
1
holoprosencephaly 3
2
holoprosencephaly 4
1
holoprosencephaly 5
5
holoprosencephaly 6
0
holoprosencephaly 7
1
holoprosencephaly 8
0
holoprosencephaly 9
1