TRAM1

protein-coding

translocation associated membrane protein 1, the group of TLC domain containing

Gene summary

This gene encodes a multi-pass membrane protein that is part of the mammalian endoplasmic reticulum. The encoded protein influences glycosylation and facilitates the translocation of secretory proteins across the endoplasmic reticulum membrane by regulating which domains of the nascent polypeptide chain are visible to the cytosol during a translocational pause. [provided by RefSeq, Oct 2009]

MANE transcript

NM_014294.6

Inheritance

—

ClinVar variants

U:43B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr8:70,573,218-70,608,416

External References & Databases

Ensembl (ENSG00000067167)

Transcript & Mutation Effects

hg38 • Region Span ~35.2 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 TRAM1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014294.6. 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	1 clinvar		3
missense			31 clinvar	3 clinvar	1 clinvar	35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	43	4	1	48

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014294.6	RefSeq	NP_055109.1	11	MANE Select
ENST00000262213.7	Ensembl	ENSP00000262213.2	11	MANE Select
NM_001317804.2	RefSeq	NP_001304733.1	11	Standard
NM_001317805.2	RefSeq	NP_001304734.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)
miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

cotranslational protein targeting to membrane
SRP-dependent cotranslational protein targeting to membrane, translocation
viral process

Molecular Function

protein binding
signaling receptor activity

Cellular Component

endoplasmic reticulum
rough endoplasmic reticulum
integral component of membrane
integral component of endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262213
Coding exons: 11
Length: 34946
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125739
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.54	134	194	0.689	0.00000956	2452
Missense (PolyPhen)		20	58.017	0.34472		820
Synonymous	-1.58	85	68.3	1.24	0.00000339	705
Loss of Function	3.70	3	21.5	0.140	0.00000114	257

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stimulatory or required for the translocation of secretory proteins across the ER membrane. {ECO:0000269|PubMed:1315422}.;

Recessive Scores

pRec: 0.156

Intolerance Scores

LoFtool: 0.203
RVIS EVS: -0.14
RVIS percentile EVS: 43.29

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.936

Gene Damage Prediction

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