TRAM2

protein-coding

translocation associated membrane protein 2, the group of TLC domain containing

Gene summary

TRAM2 is a component of the translocon, a gated macromolecular channel that controls the posttranslational processing of nascent secretory and membrane proteins at the endoplasmic reticulum (ER) membrane.[supplied by OMIM, Jul 2004]

MANE transcript

NM_012288.4

Inheritance

—

ClinVar variants

U:49B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr6:52,497,408-52,577,060

External References & Databases

Ensembl (ENSG00000065308)

Transcript & Mutation Effects

hg38 • Region Span ~79.7 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 TRAM2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012288.4. 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				2 clinvar		2
missense			46 clinvar	2 clinvar		48
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	49	4	0	53

Loading ClinVar variants...

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_012288.4	RefSeq	NP_036420.1	11	MANE Select
ENST00000182527.4	Ensembl	ENSP00000182527.3	11	MANE Select
ENST00000863425.1	Ensembl	ENSP00000533484.1	11	Standard
ENST00000863425.2	Ensembl	ENSP00000533484.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

SRP-dependent cotranslational protein targeting to membrane, translocation
collagen biosynthetic process
protein insertion into ER membrane

Molecular Function

protein binding

Cellular Component

rough endoplasmic reticulum
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000182527
Coding exons: 11
Length: 79514
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.76	145	218	0.665	0.0000125	2412
Missense (PolyPhen)		44	82.568	0.53289		958
Synonymous	0.284	83	86.4	0.961	0.00000489	710
Loss of Function	3.79	3	22.3	0.134	0.00000105	250

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Necessary for collagen type I synthesis. May couple the activity of the ER Ca(2+) pump SERCA2B with the activity of the translocon. This coupling may increase the local Ca(2+) concentration at the site of collagen synthesis, and a high Ca(2+) concentration may be necessary for the function of molecular chaperones involved in collagen folding. Required for proper insertion of the first transmembrane helix N-terminus of TM4SF20 into the ER lumen, may act as a ceramide sensor for regulated alternative translocation (RAT) (PubMed:27499293). {ECO:0000269|PubMed:14749390, ECO:0000269|PubMed:27499293}.;

Recessive Scores

pRec: 0.149

Intolerance Scores

LoFtool: 0.0398
RVIS EVS: -0.49
RVIS percentile EVS: 22.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.480

Gene Damage Prediction

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