TOM1

protein-coding

target of myb1 membrane trafficking protein, the group of MicroRNA protein coding host genes

Gene summary

This gene was identified as a target of the v-myb oncogene. The encoded protein shares its N-terminal domain in common with proteins associated with vesicular trafficking at the endosome. It is recruited to the endosomes by its interaction with endofin. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

MANE transcript

NM_005488.3

Inheritance

ClinVar variants

P:2U:106B:12

Top phenotype

Immunodeficiency 85 and autoimmunity

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr22:35,299,275-35,347,992

External References & Databases

Ensembl (ENSG00000100284)

Transcript & Mutation Effects

hg38 • Region Span ~48.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency 85 and autoimmunityLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030428

Submitter: Labcorp Genetics (formerly Invitae)

immunodeficiency 85 and autoimmunityLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0030428

Submitter: PanelApp Australia

immune system disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005046

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Immunodeficiency 85 and autoimmunityAD

Manifestation: Allergy/Immunology/Infectious; Dermatologic

Intervention: Allergy/Immunology/Infectious

Rationale: The condition can involve susceptibilty to infections, and awareness may allow preventative measures and early and aggressive treatment of infections; HSCT has been described

Refs: 31263572

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TOM1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 97

not providedTotal: 14

Immunodeficiency 85 and autoimmunityTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005488.3. 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			2 clinvar	4 clinvar	2 clinvar	8
missense	1 clinvar	1 clinvar	93 clinvar	6 clinvar		101
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	1	1	106	10	2	120

Highest pathogenic variant AF is 0.0000037180619

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 96 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005488.3	RefSeq	NP_005479.1	15	MANE Select
ENST00000449058.7	Ensembl	ENSP00000394466.2	15	MANE Select
NM_001135729.2	RefSeq	NP_001129201.1	14	Standard
NM_001135730.2	RefSeq	NP_001129202.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Innate Immune System
Immune System
EGFR1
C-MYB transcription factor network

Biological Process

intracellular protein transport
endocytosis
protein transport
endosomal transport
neutrophil degranulation

Molecular Function

protein binding
clathrin binding

Cellular Component

cytoplasm
endosome
early endosome
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000411850
Coding exons: 15
Length: 48718
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 55
Defined: 125748
p: 0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	255	308	0.827	0.0000189	3193
Missense (PolyPhen)		105	136.84	0.76732		1462
Synonymous	1.02	120	135	0.888	0.00000937	1002
Loss of Function	1.38	21	29.0	0.724	0.00000161	290

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00065	0.00065	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00026	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in intracellular trafficking. Probable association with membranes.;

Recessive Scores

pRec: 0.131

Intolerance Scores

LoFtool: 0.884
RVIS EVS: -0.55
RVIS percentile EVS: 19.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.860

Gene Damage Prediction

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