CLCN4

Chr Xp22.2

Cl-/H+ antiporter 4

Aliases:: CLC4, ClC-4
MANE:: ENST00000380833.9

OMIM: 302910 ↗NCBI: 1183 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

CLCN4 · P51793

v62025-08-01

Predicted Aligned Error matrix for CLCN4 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

84.8/ 100

Confident

760 residues

Confidence breakdown

Very high(≥ 90)49%
Confident(70–90)41%
Low(50–70)6%
Very low(< 50)5%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Disease associations (Open Targets)

X-linked non-syndromic intellectual disability
0.84
intellectual disability, X-linked 49
0.64
clcn4-related disorder
0.53
hereditary disease
0.48
non-syndromic X-linked intellectual disability
0.48
Seizure
0.27
Intellectual disability
0.15
neurodevelopmental disorder
0.15
schizophrenia
0.12
intellectual disability, X-linked 81
0.12

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

H(+)/Cl(-) exchange transporter 4

Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons (PubMed:18063579, PubMed:23647072, PubMed:25644381, PubMed:27550844, PubMed:28972156). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (PubMed:29845874). The presence of conserved gating glutamate residues is typical for family members that function as antiporters (PubMed:29845874)