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

Enables identical protein binding activity. 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, Jun 2026]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtJoubert syndrome 30

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Joubert syndrome 30 · AR · ClinGen 2023

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.05

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in ARMC9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 41

1,078 rare PASS variants

Rare truncating (LoF)

1 in 510

221 rare PASS variants

Rare synonymous (reference)

1 in 78

431 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARMC9. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 69	1 in 500
South Asian	~43k	1 in 50	1 in 290
Remaining (unassigned)	~30k	1 in 35	1 in 670
European (Finnish)	~27k	1 in 240	1 in 1,700
Admixed American	~22k	1 in 44	1 in 550
African / African American	~21k	1 in 42	1 in 410
East Asian	~20k	1 in 44	1 in 590
Ashkenazi Jewish	~13k	1 in 620	none seen
Middle Eastern	~2,884	1 in 42	1 in 360

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.