TBC1D25

protein-coding

TBC1 domain family member 25

Gene summary

This gene encodes a protein with a TBC domain and functions as a Rab GTPase activating protein. The encoded protein is involved in the fusion of autophagosomes with endosomes and lysosomes. This gene was previously known as ornithine aminotransferase-like 1, but has no similarity to ornithine aminotransferase. [provided by RefSeq, Jan 2017]

Previous symbols:

OATL1

MANE transcript

NM_002536.4

Inheritance

—

ClinVar variants

U:81B:3

Top phenotype

Abnormality of neuronal migration

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chrX:48,539,714-48,562,609

External References & Databases

Ensembl (ENSG00000068354)

Transcript & Mutation Effects

hg38 • Region Span ~22.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TBC1D25 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 4

Abnormality of neuronal migrationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002536.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	2 clinvar		8
missense			67 clinvar		1 clinvar	68
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	81	2	1	84

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002536.4	RefSeq	NP_002527.1	6	MANE Select
ENST00000376771.9	Ensembl	ENSP00000365962.4	6	MANE Select
NM_001348262.2	RefSeq	NP_001335191.1	6	Standard
NM_001348263.2	RefSeq	NP_001335192.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
TBC/RABGAPs
Membrane Trafficking
Rab regulation of trafficking

Biological Process

intracellular protein transport
autophagy
activation of GTPase activity
regulation of autophagosome maturation

Molecular Function

GTPase activator activity
protein binding
Rab GTPase binding

Cellular Component

autophagosome
cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376771
Coding exons: 6
Length: 23153
Individuals with no LoFs: 125736
Homozygous LoFs: 2
Heterozygous LoFs: 3
Defined: 125741
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.10	149	300	0.496	0.0000266	4415
Missense (PolyPhen)		38	133.88	0.28384		1955
Synonymous	0.925	115	128	0.896	0.0000111	1504
Loss of Function	3.24	4	19.4	0.206	0.00000181	255

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000050	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a GTPase-activating protein specific for RAB33B. Involved in the regulation of autophagosome maturation, the process in which autophagosomes fuse with endosomes and lysosomes. {ECO:0000269|PubMed:21383079}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.357
RVIS EVS: 0.04
RVIS percentile EVS: 57.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.549

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium