ARMC9

Chr 2

armadillo repeat containing 9

Also known as: ARM, JBTS30, KU-MEL-1, NS21

NCBI Gene: 80210 ENSG00000135931 UniProt: Q7Z3E5

The ARMC9 protein is required for ciliogenesis, specifically regulating ciliary microtubule modifications and cilium length, and acts as a positive regulator of hedgehog signaling by participating in GLI2 and GLI3 protein trafficking at the ciliary tip. Biallelic mutations cause Joubert syndrome 30, inherited in an autosomal recessive pattern. This gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, OMIM, UniProt

Predicted to be involved in cilium assembly and positive regulation of smoothened signaling pathway. Located in centriole and ciliary basal body. Implicated in Joubert syndrome 30. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.05

Clinical Summary— ARMC9

🧬

Gene-Disease Validity (ClinGen)

Joubert syndrome 30 · 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

58 unique Pathogenic / Likely Pathogenic· 345 VUS of 768 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.29

OE 0.78 (0.58–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.85Z-score

OE missense 0.88 (0.80–0.96)

333 obs / 379.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.58–1.05)

0≤0.351.4

Missense OE?0.88 (0.80–0.96)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 30 / 38.6Missense obs/exp: 333 / 379.7Syn Z: 0.19

ClinVar Variant Classifications

768 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26

Likely Pathogenic32

VUS345

Likely Benign281

Benign47

Conflicting10

Pathogenic

Likely Pathogenic

345

VUS

281

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	20	0	6	0	26
Likely Pathogenic	25	4	2	1	32
VUS	10	309	20	6	345
Likely Benign	0	11	129	141	281
Benign	1	12	23	11	47
Conflicting	—				10
Total	56	336	180	159	741

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap ARMC9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →