CALHM4

Chr 6

calcium homeostasis modulator family member 4

Also known as: C6orf78, FAM26D

NCBI Gene: 221301ENSG00000164451UniProt: Q5JW98

Predicted to enable monoatomic cation channel activity. Predicted to be involved in ATP export and monoatomic cation transmembrane transport. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

67
ClinVar variants
28
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CALHM4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 38 VUS of 67 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.67LOEUF
pLI 0.001
Z-score 0.34
OE 0.85 (0.44–1.67)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.48Z-score
OE missense 0.86 (0.71–1.04)
78 obs / 90.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.85 (0.44–1.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.71–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 5 / 5.9Missense obs/exp: 78 / 90.9Syn Z: 0.18

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic4
VUS38
Likely Benign1
24
Pathogenic
4
Likely Pathogenic
38
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
4
0
4
VUS
0
35
3
0
38
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total03631067

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

View in ClinVar →

Protein Context — Lollipop Plot

CALHM4 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools