HYDIN

Chr 16AR

HYDIN axonemal central pair apparatus protein

Also known as: CILD5, HYDIN1, PPP1R31

NCBI Gene: 54768ENSG00000157423UniProt: Q4G0P3

This gene encodes a protein that may be involved in cilia motility. Mutations in this gene cause of autosomal recessive primary ciliary dyskinesia-5, a disorder characterized by the accumulation of cerebrospinal fluid within the ventricles of the brain. A duplicate copy of this gene has been found in humans on chromosome 1. [provided by RefSeq, Jan 2013]

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 5MIM #608647
AR
576
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HYDIN
🧬
Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia 5 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 327 VUS of 576 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.51LOEUF
pLI 0.000
Z-score 7.14
OE 0.42 (0.34–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
0.81Z-score
OE missense 0.95 (0.92–0.99)
1990 obs / 2094.3 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.0.42 (0.34–0.51)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.92–0.99)
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.1.04
0≤1.21.6
LoF obs/exp: 72 / 173.5Missense obs/exp: 1990 / 2094.3Syn Z: -0.97

ClinVar Variant Classifications

576 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic41
VUS327
Likely Benign166
Benign9
Conflicting9
24
Pathogenic
41
Likely Pathogenic
327
VUS
166
Likely Benign
9
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
16
0
24
Likely Pathogenic
23
1
17
0
41
VUS
5
292
26
4
327
Likely Benign
1
57
12
96
166
Benign
0
2
4
3
9
Conflicting
—9
Total3735275103576

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

View in ClinVar →

Protein Context — Lollipop Plot

HYDIN · protein map & ClinVar variants

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

Gene2Phenotype Curations

HYDIN-related primary ciliary dyskinesia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ciliary dyskinesia, primary, 5

MIM #608647

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — HYDIN
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HYDIN mutation status as a potential predictor of immune checkpoint inhibitor efficacy in melanoma.
Li L et al.·Aging (Albany NY)
2023
Robust detection of pathogenic HYDIN variants that cause primary ciliary dyskinesia using RNA-seq of nasal mucosa.
Hijikata M et al.·J Med Genet
2025
Genetics of 67 patients of suspected primary ciliary dyskinesia from India.
Jat KR et al.·Clin Genet
2024Cohort
HYDIN loss-of-function inhibits GATA4 expression and enhances atrial septal defect risk.
Cao Y et al.·Mech Dev
2020
In situ structure of the mouse sperm central apparatus reveals mechanistic insights into asthenozoospermia.
Zhu Y et al.·Cell Res
2025Functional
Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype.
Staar BO et al.·Cells
2023
[Primary ciliary dyskinesia with HYDIN gene mutations in a child and literature review].
Chen LL et al.·Zhonghua Er Ke Za Zhi
2017Review
Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects.
Bolkier Y et al.·J Med Genet
2022
Novel HYDIN variants associated with male infertility in two Chinese families.
Yu H et al.·Front Endocrinol (Lausanne)
2023Case report
Combined approaches, including long-read sequencing, address the diagnostic challenge of HYDIN in primary ciliary dyskinesia.
Fleming A et al.·Eur J Hum Genet
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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