TOM1L2

protein-coding

target of myb1 like 2 membrane trafficking protein

Gene summary

This gene belongs to a small gene family whose members have an N-terminal VHS domain followed by a GAT domain; domains which typically participate in vesicular trafficking. The canonical protein encoded by this gene also has a C-terminal clathrin binding motif. This protein has been shown to interact with Tollip, clathrin and ubiquitin and is thought to play a role in endosomal sorting. This gene resides in the 3.7 Mb deletion of chromosome region 17p11.2 that is associated with Smith-Magenis syndrome. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Apr 2017]

MANE transcript

NM_001082968.2

Inheritance

—

ClinVar variants

U:79B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr17:17,843,507-17,972,422

External References & Databases

Ensembl (ENSG00000175662)

Transcript & Mutation Effects

hg38 • Region Span ~128.9 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 TOM1L2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 75

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001082968.2. 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			1 clinvar			1
missense			77 clinvar	2 clinvar		79
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	79	2	0	81

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 97 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001082968.2	RefSeq	NP_001076437.1	15	MANE Select
ENST00000379504.8	Ensembl	ENSP00000368818.3	15	MANE Select
NM_001033551.3	RefSeq	NP_001028723.1	14	Standard
NM_001288786.2	RefSeq	NP_001275715.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fibroblast growth factor-1
EGFR1

Biological Process

intracellular protein transport
signal transduction
negative regulation of mitotic nuclear division

Molecular Function

protein binding
protein kinase binding
clathrin binding

Cellular Component

cell
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379504
Coding exons: 15
Length: 128909
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.678	280	314	0.892	0.0000187	3293
Missense (PolyPhen)		76	89.62	0.84802		971
Synonymous	-0.730	137	127	1.08	0.00000825	1024
Loss of Function	3.53	11	32.8	0.335	0.00000208	313

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable role in protein transport. May regulate growth factor-induced mitogenic signaling. {ECO:0000269|PubMed:16412388, ECO:0000269|PubMed:16479011}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.547
RVIS EVS: -1.16
RVIS percentile EVS: 6.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.921

Gene Damage Prediction

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