TMEM204

Chr 16

transmembrane protein 204

Also known as: C16orf30, CLP24

NCBI Gene: 79652 ENSG00000131634 OMIM: 611002

The TMEM204 protein regulates paracellular permeability and participates in cell-cell interactions through adherens junctions. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, which typically presents in infancy with seizures and developmental delays. This gene is highly constrained against loss-of-function variants, indicating its critical importance for normal cellular function.

OMIM ResearchSummary from RefSeq, UniProt

C16ORF30 plays a role in cell adhesion and cellular permeability at adherens junctions (Kearsey et al., 2004 [PubMed 15206924]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.38

Clinical Summary— TMEM204

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 35 VUS of 53 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.913

Z-score 2.60

OE 0.00 (0.00–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.99Z-score

OE missense 0.78 (0.67–0.90)

124 obs / 159.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.38)

0≤0.351.4

Missense OE?0.78 (0.67–0.90)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 0 / 7.8Missense obs/exp: 124 / 159.3Syn Z: -0.28

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS35

Likely Benign7

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	34	1	0	35
Likely Benign	0	3	0	4	7
Benign	0	0	0	0	0
Total	1	37	1	4	43

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 57) ClinVar copy-number / structural variants overlap TMEM204 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →