TMEM208

protein-coding

transmembrane protein 208

Gene summary

This gene encodes a highly conserved protein which is localized in the endoplasmic reticulum (ER). The protein is linked to autophagy and ER stress. Knockdown of this gene increased autophagy and triggered ER stress. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MANE transcript

NM_014187.4

Inheritance

—

ClinVar variants

U:34B:1

Top phenotype

TMEM208-related condition

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr16:67,227,103-67,229,278

External References & Databases

Ensembl (ENSG00000168701)

Transcript & Mutation Effects

hg38 • Region Span ~2.2 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 TMEM208 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 28

TMEM208-related conditionTotal: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014187.4. 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			1 clinvar		1 clinvar	2
missense			30 clinvar			30
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	34	0	1	35

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014187.4	RefSeq	NP_054906.2	6	MANE Select
ENST00000304800.14	Ensembl	ENSP00000305892.9	6	MANE Select
NM_001318217.2	RefSeq	NP_001305146.1	3	Standard
ENST00000562235.5	Ensembl	ENSP00000457502.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

vacuolar protein processing
autophagy

Cellular Component

vacuole
endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304800
Coding exons: 6
Length: 2176
Individuals with no LoFs: 124621
Homozygous LoFs: 0
Heterozygous LoFs: 41
Defined: 124662
p: 0.000164

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.569	86	102	0.842	0.00000601	1112
Missense (PolyPhen)		26	35.31	0.73634		437
Synonymous	-0.350	41	38.2	1.07	0.00000203	337
Loss of Function	1.39	6	10.9	0.548	5.66e-7	116

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.00036	0.00035	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00039	0.00039	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00017	0.00016	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function as a negative regulator of endoplasmic reticulum-stress induced autophagy. {ECO:0000269|PubMed:23691174}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.669
RVIS EVS: -0.12
RVIS percentile EVS: 44.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.755

Gene Damage Prediction

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