AXDND1

Chr 1

axonemal dynein light chain domain containing 1

Also known as: C1orf125

NCBI Gene: 126859 ENSG00000162779 UniProt: Q5T1B0

Predicted to be involved in manchette assembly. Located in ciliary basal body and cytosol. [provided by Alliance of Genome Resources, Jul 2025]

Research

Predicted to be involved in manchette assembly. Located in ciliary basal body and cytosol. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.99

Clinical Summary— AXDND1

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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

51 unique Pathogenic / Likely Pathogenic· 183 VUS of 370 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.61

OE 0.78 (0.61–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.30Z-score

OE missense 1.04 (0.96–1.12)

516 obs / 497.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.78 (0.61–0.99)

0≤0.351.4

Missense OE?1.04 (0.96–1.12)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 47 / 60.5Missense obs/exp: 516 / 497.3Syn Z: 0.15

This gene — mechanism propensity

0.6840th %ile

GOF

0.73top 25%

LOF

0.3745th %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

370 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic43

VUS183

Likely Benign95

Benign17

Conflicting10

Pathogenic

Likely Pathogenic

183

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	2	1	0	8
Likely Pathogenic	27	16	0	0	43
VUS	2	166	13	2	183
Likely Benign	0	11	30	54	95
Benign	0	0	16	1	17
Conflicting	—				10
Total	34	195	60	57	356

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap AXDND1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →