TBC1D3C (TBC1 domain family member 3C) - Rat Genome Database

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Gene: TBC1D3C (TBC1 domain family member 3C) Homo sapiens
Analyze
No known orthologs.
Symbol: TBC1D3C
Name: TBC1 domain family member 3C
RGD ID: 1605182
HGNC Page HGNC:24889
Description: Predicted to enable GTPase activator activity. Predicted to be located in early endosome membrane.
Type: protein-coding
RefSeq Status: REVIEWED
Previously known as: FLJ78248; MGC44903; PRC17; Rab GTPase-activating protein PRC17; TBC1 domain family member 3; TBC1 domain family member 3C-like protein ENSP00000341742; TBC1 domain family member 3C/3D; TBC1 domain family, member 3C; TBC1D3; TBC1D3A; TBC1D3D; telomeric TBC1 domain family member 3-like
RGD Orthologs
Alliance Orthologs
More Info homologs ...
Related Pseudogenes: LOC100420289  
Allele / Splice: See ClinVar data
Latest Assembly: GRCh38 - Human Genome Assembly GRCh38
Position:
Human AssemblyChrPosition (strand)SourceGenome Browsers
JBrowseNCBIUCSCEnsembl
GRCh381738,057,693 - 38,070,301 (-)NCBIGRCh38GRCh38hg38GRCh38
GRCh38.p14 Ensembl1738,057,693 - 38,068,634 (-)EnsemblGRCh38hg38GRCh38
GRCh371734,581,085 - 34,592,022 (-)NCBIGRCh37GRCh37hg19GRCh37
Build 361731,605,198 - 31,616,140 (-)NCBINCBI36Build 36hg18NCBI36
Celera1754,549,000 - 54,559,962 (-)NCBICelera
Cytogenetic Map17q12NCBI
HuRef1730,678,615 - 30,683,489 (-)NCBIHuRef
CHM1_11734,645,210 - 34,656,134 (-)NCBICHM1_1
JBrowse: View Region in Genome Browser (JBrowse)
Model


Disease Annotations     Click to see Annotation Detail View

Gene-Chemical Interaction Annotations     Click to see Annotation Detail View
Gene Ontology Annotations     Click to see Annotation Detail View

Biological Process

Cellular Component

Molecular Function

References

References - curated
# Reference Title Reference Citation
1. ClinVar Automated Import and Annotation Pipeline RGD automated import pipeline for ClinVar variants, variant-to-disease annotations and gene-to-disease annotations
2. Data Import for Chemical-Gene Interactions RGD automated import pipeline for gene-chemical interactions
Additional References at PubMed
PMID:8889549   PMID:12477932   PMID:12604796   PMID:16863688   PMID:21873635   PMID:28700943   PMID:32296183   PMID:34373451  


Genomics

Variants

.
Variants in TBC1D3C
9 total Variants

Clinical Variants
Name Type Condition(s) Position(s) Clinical significance
GRCh38/hg38 17q21.33-24.2(chr17:36449220-68170214)x3 copy number gain See cases [RCV000050957] Chr17:36449220..68170214 [GRCh38]
Chr17:48563237..65936105 [GRCh37]
Chr17:45918236..63677950 [NCBI36]
Chr17:17q21.33-24.2
pathogenic
GRCh38/hg38 17q23.2-25.3(chr17:36449220-83086677)x3 copy number gain Developmental Delay and additional significant developmental and morphological phenotypes referred for genetic testing [RCV000052483]|Developmental delay and additional significant developmental and morphological phenotypes referred for genetic testing [RCV000052483]|See cases [RCV000052483] Chr17:36449220..83086677 [GRCh38]
Chr17:58617905..81044553 [GRCh37]
Chr17:55972687..78637842 [NCBI36]
Chr17:17q23.2-25.3
pathogenic
GRCh37/hg19 17q12(chr17:34437475-36243028) copy number gain Polyhydramnios [RCV001291974] Chr17:34437475..36243028 [GRCh37]
Chr17:17q12
pathogenic
GRCh38/hg38 17q23.1-25.1(chr17:36449220-75053130)x3 copy number gain See cases [RCV000137437] Chr17:36449220..75053130 [GRCh38]
Chr17:57595736..73049225 [GRCh37]
Chr17:54950518..70560820 [NCBI36]
Chr17:17q23.1-25.1
pathogenic
GRCh37/hg19 17q12(chr17:34450405-36248918)x1 copy number loss See cases [RCV000133661] Chr17:34450405..36248918 [GRCh37]
Chr17:31474518..33323031 [NCBI36]
Chr17:17q12
pathogenic
GRCh37/hg19 17q12(chr17:34431767-34775684)x3 copy number gain See cases [RCV000139674] Chr17:34431767..34775684 [GRCh37]
Chr17:31455880..31849797 [NCBI36]
Chr17:17q12
likely benign
GRCh38/hg38 17q12(chr17:36446545-38225796)x1 copy number loss See cases [RCV000137918] Chr17:36446545..38225796 [GRCh38]
Chr17:34817422..36263019 [GRCh37]
Chr17:31891535..33635633 [NCBI36]
Chr17:17q12
pathogenic
GRCh38/hg38 17q12(chr17:38019086-38143043)x3 copy number gain See cases [RCV000138874] Chr17:38019086..38143043 [GRCh38]
Chr17:33406244..33635615 [NCBI36]
Chr17:17q12
likely benign
GRCh38/hg38 17q12(chr17:36357258-38225796)x3 copy number gain See cases [RCV000138816] Chr17:36357258..38225796 [GRCh38]
Chr17:34611352..36263019 [GRCh37]
Chr17:31635465..33635633 [NCBI36]
Chr17:17q12
likely pathogenic
NC_000017.10:g.(34360227_34437475)_(36214026_36473024)del deletion Chromosome 17q12 deletion syndrome [RCV000191150] Chr17:34437475..36214026 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17q12(chr17:34425362-36410559)x3 copy number gain See cases [RCV000447719] Chr17:34425362..36410559 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17q12(chr17:34437482-36404555)x3 copy number gain See cases [RCV000510217] Chr17:34437482..36404555 [GRCh37]
Chr17:17q12
likely pathogenic
GRCh37/hg19 17q12(chr17:34437482-36350584)x3 copy number gain See cases [RCV000511415] Chr17:34437482..36350584 [GRCh37]
Chr17:17q12
likely pathogenic
GRCh37/hg19 17p13.3-q25.3(chr17:526-81041938) copy number gain See cases [RCV000511439] Chr17:526..81041938 [GRCh37]
Chr17:17p13.3-q25.3
pathogenic
GRCh37/hg19 17q12(chr17:34447113-36283612)x1 copy number loss See cases [RCV000510761] Chr17:34447113..36283612 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17q12(chr17:34475679-36283612)x1 copy number loss See cases [RCV000510867] Chr17:34475679..36283612 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17p13.3-q25.3(chr17:526-81041938)x3 copy number gain See cases [RCV000512441] Chr17:526..81041938 [GRCh37]
Chr17:17p13.3-q25.3
pathogenic
GRCh37/hg19 17q12(chr17:34426244-36225988)x3 copy number gain not provided [RCV000683921] Chr17:34426244..36225988 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17q12(chr17:34475679-36311009)x1 copy number loss not provided [RCV000683922] Chr17:34475679..36311009 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17q12(chr17:34425362-36283612)x3 copy number gain not provided [RCV000683920] Chr17:34425362..36283612 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17q12(chr17:34477385-36404555)x1 copy number loss not provided [RCV000683923] Chr17:34477385..36404555 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17p13.3-q25.3(chr17:8547-81060040)x3 copy number gain not provided [RCV000739324] Chr17:8547..81060040 [GRCh37]
Chr17:17p13.3-q25.3
pathogenic
GRCh37/hg19 17p13.3-q25.3(chr17:7214-81058310)x3 copy number gain not provided [RCV000739320] Chr17:7214..81058310 [GRCh37]
Chr17:17p13.3-q25.3
pathogenic
GRCh37/hg19 17p13.3-q25.3(chr17:12344-81057996)x3 copy number gain not provided [RCV000739325] Chr17:12344..81057996 [GRCh37]
Chr17:17p13.3-q25.3
pathogenic
GRCh37/hg19 17q12(chr17:34438213-34941924)x3 copy number gain not provided [RCV000752018] Chr17:34438213..34941924 [GRCh37]
Chr17:17q12
benign
GRCh37/hg19 17q12(chr17:34443811-34819191)x3 copy number gain not provided [RCV000752019] Chr17:34443811..34819191 [GRCh37]
Chr17:17q12
benign
GRCh37/hg19 17q12(chr17:34443811-34823170)x3 copy number gain not provided [RCV000752020] Chr17:34443811..34823170 [GRCh37]
Chr17:17q12
benign
GRCh37/hg19 17q12(chr17:34443811-34917969)x4 copy number gain not provided [RCV000752021] Chr17:34443811..34917969 [GRCh37]
Chr17:17q12
benign
GRCh37/hg19 17q12(chr17:34445325-34917969)x3 copy number gain not provided [RCV000752022] Chr17:34445325..34917969 [GRCh37]
Chr17:17q12
benign
GRCh37/hg19 17q12(chr17:34437475-36214026) copy number gain Chromosome 17q12 duplication syndrome [RCV000767740] Chr17:34437475..36214026 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17p11.2-q21.2(chr17:21690653-38772647)x3 copy number gain not provided [RCV000846852] Chr17:21690653..38772647 [GRCh37]
Chr17:17p11.2-q21.2
pathogenic
GRCh37/hg19 17q12(chr17:34405241-34823294)x1 copy number loss not provided [RCV001259893] Chr17:34405241..34823294 [GRCh37]
Chr17:17q12
uncertain significance
GRCh37/hg19 17q12(chr17:34463923-36410559) copy number loss Chromosome 17q12 deletion syndrome [RCV002280707] Chr17:34463923..36410559 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17q12(chr17:34425363-36404555)x3 copy number gain not provided [RCV002472574] Chr17:34425363..36404555 [GRCh37]
Chr17:17q12
pathogenic
NM_001001418.6(TBC1D3C):c.1481A>G (p.Gln494Arg) single nucleotide variant not specified [RCV004216139] Chr17:38058177 [GRCh38]
Chr17:17q12
uncertain significance
NM_001001418.6(TBC1D3C):c.1439T>C (p.Val480Ala) single nucleotide variant not specified [RCV004184879] Chr17:38058219 [GRCh38]
Chr17:17q12
uncertain significance
NM_001001418.6(TBC1D3C):c.1519G>A (p.Ala507Thr) single nucleotide variant not specified [RCV004186639] Chr17:38058139 [GRCh38]
Chr17:17q12
likely benign
NM_001001418.6(TBC1D3C):c.97G>A (p.Asp33Asn) single nucleotide variant not specified [RCV004181866] Chr17:38066808 [GRCh38]
Chr17:17q12
uncertain significance
NM_001001418.6(TBC1D3C):c.350= (p.Thr117=) variation not specified [RCV004202460] Chr17:38064347 [GRCh38]
Chr17:17q12
likely benign
NM_001001418.6(TBC1D3C):c.1231C>T (p.Arg411Cys) single nucleotide variant not specified [RCV004246589] Chr17:38058427 [GRCh38]
Chr17:17q12
uncertain significance
NM_001001418.6(TBC1D3C):c.1154G>C (p.Gly385Ala) single nucleotide variant not specified [RCV004075684] Chr17:38058504 [GRCh38]
Chr17:17q12
uncertain significance
NM_001001418.6(TBC1D3C):c.583G>A (p.Ala195Thr) single nucleotide variant not specified [RCV004189261] Chr17:38061987 [GRCh38]
Chr17:17q12
uncertain significance
NM_001001418.6(TBC1D3C):c.1195C>T (p.Arg399Trp) single nucleotide variant not specified [RCV004219660] Chr17:38058463 [GRCh38]
Chr17:17q12
uncertain significance
NM_001001418.6(TBC1D3C):c.967C>T (p.Arg323Cys) single nucleotide variant not specified [RCV004219621] Chr17:38059672 [GRCh38]
Chr17:17q12
uncertain significance
GRCh37/hg19 17q11.2-12(chr17:30572862-35843988) copy number loss Chromosome 17q12 deletion syndrome [RCV003319594] Chr17:30572862..35843988 [GRCh37]
Chr17:17q11.2-12
pathogenic
GRCh37/hg19 17q12(chr17:34440083-36410559)x3 copy number gain not provided [RCV003485154] Chr17:34440083..36410559 [GRCh37]
Chr17:17q12
pathogenic
GRCh37/hg19 17q12(chr17:34425362-36371146)x3 copy number gain not specified [RCV003987227] Chr17:34425362..36371146 [GRCh37]
Chr17:17q12
pathogenic
miRNA Target Status

Predicted Target Of
Summary Value
Count of predictions:2195
Count of miRNA genes:749
Interacting mature miRNAs:872
Transcripts:ENST00000308078, ENST00000336331, ENST00000398688, ENST00000451448, ENST00000457979, ENST00000585570, ENST00000588590, ENST00000591555
Prediction methods:Microtar, Miranda, Rnahybrid
Result types:miRGate_prediction

The detailed report is available here: Full Report CSV TAB Printer

miRNA Target Status data imported from miRGate (http://mirgate.bioinfo.cnio.es/).
For more information about miRGate, see PMID:25858286 or access the full paper here.

Markers in Region
D17S1360E  
Human AssemblyChrPosition (strand)SourceJBrowse
Cytogenetic Map17q23.2UniSTS
Cytogenetic Map17q12UniSTS
RH10527  
Human AssemblyChrPosition (strand)SourceJBrowse
Cytogenetic Map17q23.2UniSTS
Cytogenetic Map17q12UniSTS
G19723  
Human AssemblyChrPosition (strand)SourceJBrowse
Cytogenetic Map17q23.2UniSTS
Cytogenetic Map17q12UniSTS


Expression


RNA-SEQ Expression
High: > 1000 TPM value   Medium: Between 11 and 1000 TPM
Low: Between 0.5 and 10 TPM   Below Cutoff: < 0.5 TPM

alimentary part of gastrointestinal system circulatory system endocrine system exocrine system hemolymphoid system hepatobiliary system integumental system musculoskeletal system nervous system renal system reproductive system respiratory system sensory system adipose tissue appendage entire extraembryonic component
High
Medium
Low 4 4 1 8 4 9 15 8 2 4
Below cutoff 632 665 473 120 379 63 1230 539 1354 38 588 420 60 318 813 1

Sequence


RefSeq Acc Id: ENST00000610580   ⟹   ENSP00000479418
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh38.p14 Ensembl1736,172,886 - 36,176,592 (-)Ensembl
RefSeq Acc Id: ENST00000611257   ⟹   ENSP00000478473
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh38.p14 Ensembl1736,165,683 - 36,176,636 (-)Ensembl
RefSeq Acc Id: ENST00000616006   ⟹   ENSP00000478440
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh38.p14 Ensembl1736,172,294 - 36,176,636 (-)Ensembl
RefSeq Acc Id: ENST00000620215   ⟹   ENSP00000478683
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh38.p14 Ensembl1738,181,659 - 38,192,555 (-)Ensembl
RefSeq Acc Id: ENST00000622206   ⟹   ENSP00000482345
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh38.p14 Ensembl1738,057,693 - 38,068,634 (-)Ensembl
RefSeq Acc Id: ENST00000622280
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh38.p14 Ensembl1736,170,071 - 36,172,652 (-)Ensembl
RefSeq Acc Id: NM_001001418   ⟹   NP_001001418
RefSeq Status: REVIEWED
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh381738,057,693 - 38,068,634 (-)NCBI
GRCh371734,581,085 - 34,592,039 (-)NCBI
Build 361731,605,198 - 31,616,140 (-)NCBI Archive
HuRef1730,678,615 - 30,683,489 (-)NCBI
CHM1_11736,449,256 - 36,460,197 (-)NCBI
Sequence:
RefSeq Acc Id: XM_006721904   ⟹   XP_006721967
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh381738,057,693 - 38,068,489 (-)NCBI
Sequence:
RefSeq Acc Id: XM_006721905   ⟹   XP_006721968
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh381738,057,693 - 38,068,489 (-)NCBI
Sequence:
RefSeq Acc Id: XM_006721907   ⟹   XP_006721970
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh381738,057,693 - 38,068,489 (-)NCBI
Sequence:
RefSeq Acc Id: XM_006721908   ⟹   XP_006721971
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh381738,059,620 - 38,068,489 (-)NCBI
Sequence:
RefSeq Acc Id: XM_011524814   ⟹   XP_011523116
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh381738,057,693 - 38,068,634 (-)NCBI
Sequence:
RefSeq Acc Id: XM_047436082   ⟹   XP_047292038
Type: CODING
Position:
Human AssemblyChrPosition (strand)Source
GRCh381738,057,693 - 38,070,301 (-)NCBI
RefSeq Acc Id: NP_001001418   ⟸   NM_001001418
- UniProtKB: Q9H0B9 (UniProtKB/Swiss-Prot),   Q6DCB4 (UniProtKB/Swiss-Prot),   A8K007 (UniProtKB/Swiss-Prot),   A6NGX2 (UniProtKB/Swiss-Prot),   Q9UDD4 (UniProtKB/Swiss-Prot),   Q8IZP1 (UniProtKB/Swiss-Prot),   Q6IPX1 (UniProtKB/Swiss-Prot),   B2R8D7 (UniProtKB/TrEMBL)
- Sequence:
RefSeq Acc Id: XP_006721968   ⟸   XM_006721905
- Peptide Label: isoform X2
- UniProtKB: B2R8D7 (UniProtKB/TrEMBL)
- Sequence:
RefSeq Acc Id: XP_006721967   ⟸   XM_006721904
- Peptide Label: isoform X1
- UniProtKB: B2R8D7 (UniProtKB/TrEMBL)
- Sequence:
RefSeq Acc Id: XP_006721970   ⟸   XM_006721907
- Peptide Label: isoform X4
- UniProtKB: B2R8D7 (UniProtKB/TrEMBL)
- Sequence:
RefSeq Acc Id: XP_006721971   ⟸   XM_006721908
- Peptide Label: isoform X5
- Sequence:
RefSeq Acc Id: XP_011523116   ⟸   XM_011524814
- Peptide Label: isoform X1
- UniProtKB: B2R8D7 (UniProtKB/TrEMBL)
- Sequence:
RefSeq Acc Id: ENSP00000482345   ⟸   ENST00000622206
RefSeq Acc Id: ENSP00000478440   ⟸   ENST00000616006
RefSeq Acc Id: ENSP00000478473   ⟸   ENST00000611257
RefSeq Acc Id: ENSP00000479418   ⟸   ENST00000610580
RefSeq Acc Id: XP_047292038   ⟸   XM_047436082
- Peptide Label: isoform X3
- UniProtKB: Q9H0B9 (UniProtKB/Swiss-Prot),   Q8IZP1 (UniProtKB/Swiss-Prot),   Q6DCB4 (UniProtKB/Swiss-Prot),   A8K007 (UniProtKB/Swiss-Prot),   A6NGX2 (UniProtKB/Swiss-Prot),   Q9UDD4 (UniProtKB/Swiss-Prot),   Q6IPX1 (UniProtKB/Swiss-Prot)
RefSeq Acc Id: ENSP00000478683   ⟸   ENST00000620215
Protein Domains
Rab-GAP TBC

Protein Structures
Name Modeler Protein Id AA Range Protein Structure
AF-Q6IPX1-F1-model_v2 AlphaFold Q6IPX1 1-549 view protein structure
AF-Q8IZP1-F1-model_v2 AlphaFold Q8IZP1 1-549 view protein structure


Additional Information

Database Acc Id Source(s)
AGR Gene HGNC:24889 AgrOrtholog
COSMIC TBC1D3C COSMIC
Ensembl Genes ENSG00000274611 Ensembl, UniProtKB/Swiss-Prot
  ENSG00000274808 Ensembl
  ENSG00000278299 Ensembl, ENTREZGENE, UniProtKB/Swiss-Prot
Ensembl Transcript ENST00000620215.3 UniProtKB/Swiss-Prot
  ENST00000622206 ENTREZGENE
  ENST00000622206.2 UniProtKB/Swiss-Prot
Gene3D-CATH putative rabgap domain of human tbc1 domain family member 14 like domains UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  Ypt/Rab-GAP domain of gyp1p, domain 1 UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  Ypt/Rab-GAP domain of gyp1p, domain 3 UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
GTEx ENSG00000274611 GTEx
  ENSG00000274808 GTEx
  ENSG00000278299 GTEx
HGNC ID HGNC:24889 ENTREZGENE
Human Proteome Map TBC1D3C Human Proteome Map
InterPro Rab-GAP-TBC_dom UniProtKB/TrEMBL
  Rab-GAP_TBC_sf UniProtKB/TrEMBL
  Rab-GTPase-TBC_dom UniProtKB/Swiss-Prot
  Rab-GTPase_TBC_sf UniProtKB/Swiss-Prot
KEGG Report hsa:101060321 UniProtKB/Swiss-Prot
  hsa:414060 UniProtKB/Swiss-Prot
  hsa:729873 UniProtKB/Swiss-Prot
NCBI Gene 414060 ENTREZGENE
OMIM 610806 OMIM
PANTHER RAB GTPASE-ACTIVATING PROTEIN 1 UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
  RAB GTPASE-ACTIVATING PROTEIN 1-LIKE UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
Pfam RabGAP-TBC UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
PharmGKB PA142670834 PharmGKB
PROSITE TBC_RABGAP UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
SMART TBC UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
Superfamily-SCOP SSF47923 UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
UniProt A6NGX2 ENTREZGENE
  A8K007 ENTREZGENE
  B2R8D7 ENTREZGENE, UniProtKB/TrEMBL
  Q6DCB4 ENTREZGENE
  Q6IPX1 ENTREZGENE
  Q8IZP1 ENTREZGENE
  Q9H0B9 ENTREZGENE
  Q9UDD4 ENTREZGENE
  TBC3A_HUMAN UniProtKB/Swiss-Prot
  TBC3C_HUMAN UniProtKB/Swiss-Prot
UniProt Secondary A6NGX2 UniProtKB/Swiss-Prot
  A8K007 UniProtKB/Swiss-Prot
  Q6DCB4 UniProtKB/Swiss-Prot
  Q9H0B9 UniProtKB/Swiss-Prot
  Q9UDD4 UniProtKB/Swiss-Prot


Nomenclature History
Date Current Symbol Current Name Previous Symbol Previous Name Description Reference Status
2015-11-24 TBC1D3C  TBC1 domain family member 3C    TBC1 domain family, member 3C  Symbol and/or name change 5135510 APPROVED