CALHM6

Chr 6

calcium homeostasis modulator family member 6

Also known as: C6orf187, FAM26F, INAM, dJ93H18.5

NCBI Gene: 441168 ENSG00000188820 UniProt: Q5R3K3

Predicted to enable monoatomic cation channel activity. Predicted to be involved in ATP export; monoatomic cation transmembrane transport; and regulation of natural killer cell cytokine production. Predicted to be located in immunological synapse. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

0.2

Missense Z

1.77

LOEUF

Clinical Summary— CALHM6

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

28 Pathogenic / Likely Pathogenic· 49 VUS of 79 total submissions

💊

Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

1.77LOEUF

pLI 0.009

Z-score 0.31

OE 0.82 (0.36–1.77)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

0.19Z-score

OE missense 0.95 (0.82–1.10)

128 obs / 134.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.82 (0.36–1.77)

0≤0.351.4

Missense OE0.95 (0.82–1.10)

0≤0.61.4

Synonymous OE0.88

0≤1.21.6

LoF obs/exp: 3 / 3.6Missense obs/exp: 128 / 134.3Syn Z: 0.74

DNGOF

Badonyi & Marsh 2024 ↗

0.74top 25%

GOF

0.74top 25%

LOF

0.2190th %ile

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

DNprediction above median

GOFprediction 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

79 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24

Likely Pathogenic4

VUS49

Likely Benign2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	24	0	24
Likely Pathogenic	0	4	0	4
VUS	47	2	0	49
Likely Benign	1	0	1	2
Benign	0	0	0	0
Total	48	30	1	79

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

View in ClinVar →

CALHM6 · protein map & ClinVar variants

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

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Single Cell Sequencing TechnologyGene Expression ProfilingGene Expression

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA. a Prospective Study Will Evaluate the Performance of Direct LS-TA in Triage Febrile Patients Into Major Categories of Infections: Viral, Bacterial or Active Tuberculosis.

NOT YET RECRUITING

NCT06846645Chinese University of Hong KongStarted 2025-02

No intervention

Gene ExpressionGene Expression ProfilingInfection

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA

ACTIVE NOT RECRUITING

NCT06838780Chinese University of Hong KongStarted 2018-01-01

No intervention

Clinical Literature

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3