TMEM107

Chr 17AR

transmembrane protein 107

Also known as: GRVS638, JBTS29, MKS13, PRO1268

NCBI Gene: 84314 ENSG00000179029 UniProt: Q6UX40 OMIM: 616183

This gene encodes a transmembrane protein that is a component of the primary cilia transition zone and regulates ciliogenesis and ciliary protein composition. Mutations cause autosomal recessive ciliopathies including Meckel syndrome, Joubert syndrome, and orofaciodigital syndrome. The gene shows high constraint against loss-of-function variants, reflecting its critical role in ciliary function and embryonic development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a transmembrane protein and component of the primary cilia transition zone. The encoded protein regulates ciliogenesis and ciliary protein composition. Human fibroblasts expressing a mutant allele of this gene exhibit reduced numbers of cilia, altered cilia length, and impaired sonic hedgehog signaling. In human patients, different mutations in this gene cause different ciliopathies, including Meckel-Gruber syndrome and orofaciodigital syndrome. [provided by RefSeq, May 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.903 OMIM phenotypes

Clinical Summary— TMEM107

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

34 unique Pathogenic / Likely Pathogenic· 164 VUS of 318 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — TMEM107

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?

1.90LOEUF

pLI 0.000

Z-score -0.91

OE 1.36 (0.82–1.90)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.09Z-score

OE missense 0.67 (0.54–0.83)

58 obs / 86.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.36 (0.82–1.90)

0≤0.351.4

Missense OE?0.67 (0.54–0.83)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 10 / 7.3Missense obs/exp: 58 / 86.6Syn Z: 0.68

This gene — mechanism propensity

0.6453th %ile

GOF

0.75top 25%

LOF

0.3066th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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

318 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25

Likely Pathogenic9

VUS164

Likely Benign70

Benign30

Conflicting16

Pathogenic

Likely Pathogenic

164

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	2	17	0	25
Likely Pathogenic	1	0	8	0	9
VUS	4	40	120	0	164
Likely Benign	0	0	47	23	70
Benign	0	0	28	2	30
Conflicting	—				16
Total	11	42	220	25	314

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap TMEM107 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →