TMEM222

Chr 1AR

transmembrane protein 222

Also known as: C1orf160, NEDMOSBA

TMEM222 encodes a protein localized to dendrites, though its specific cellular function remains unclear. Biallelic mutations cause a neurodevelopmental disorder with motor and speech delay and behavioral abnormalities, inherited in an autosomal recessive pattern. The gene shows relatively low constraint to loss-of-function variants (pLI 0.000004), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, OMIM
LOFmechanismARLOEUF 1.491 OMIM phenotype
Clinical SummaryTMEM222
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.49LOEUF
pLI 0.000
Z-score 0.43
OE 0.86 (0.521.49)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.44Z-score
OE missense 0.89 (0.761.04)
111 obs / 124.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.86 (0.521.49)
00.351.4
Missense OE0.89 (0.761.04)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 9 / 10.5Missense obs/exp: 111 / 124.7Syn Z: 0.80
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTMEM222-related neurodevelopmental disorder with motor and speech delay and behavioural abnormalitiesLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5476th %ile
GOF
0.76top 25%
LOF
0.4037th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TMEM222 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found