TMEM165

Chr 4AR

transmembrane protein 165

Also known as: CDG2K, FT27, GDT1, SLC64A1, TMPT27, TPARL

NCBI Gene: 55858ENSG00000134851UniProt: Q9HC07

This gene encodes a predicted transmembrane protein with a perinuclear Golgi-like distribution in fibroblasts. Mutations in this gene are associated with the autosomal recessive disorder congenital disorder of glycosylation, type IIk. Knockdown of this gene's expression causes decreased sialylation in HEK cells and suggests this gene plays a role in terminal Golgi glycosylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IIkMIM #614727
AR
0
Active trials
24
Pathogenic / LP
269
ClinVar variants
4
Pubs (1 yr)
1.4
Missense Z
0.63
LOEUF
Clinical Summary— TMEM165
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 138 VUS of 269 total submissions
📖
GeneReview available — TMEM165
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.63LOEUF
pLI 0.283
Z-score 2.46
OE 0.24 (0.11–0.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.37Z-score
OE missense 0.70 (0.60–0.82)
117 obs / 166.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.11–0.63)
0≤0.351.4
Missense OE0.70 (0.60–0.82)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 3 / 12.3Missense obs/exp: 117 / 166.6Syn Z: 0.47
DN
DN
0.73top 25%
GOF
0.6150th %ile
LOF
0.3261th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

269 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic1
VUS138
Likely Benign80
Benign23
Conflicting4
23
Pathogenic
1
Likely Pathogenic
138
VUS
80
Likely Benign
23
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
21
0
23
Likely Pathogenic
0
0
1
0
1
VUS
1
123
14
0
138
Likely Benign
0
1
36
43
80
Benign
0
0
20
3
23
Conflicting
—4
Total11269246269

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

TMEM165 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TMEM165-related congenital disorder of glycosylation

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients