ARMC9

protein-coding

armadillo repeat containing 9, the group of MicroRNA protein coding host genes|Armadillo repeat containing

Gene summary

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]

MANE transcript

NM_001352754.2

Inheritance

ClinVar variants

P:62U:334B:183

Top phenotype

Joubert syndrome 30

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr2:231,198,546-231,376,848

External References & Databases

Ensembl (ENSG00000135931)

Transcript & Mutation Effects

hg38 • Region Span ~178.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Joubert syndrome 30DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0033308

Submitter: ClinGen

*ARMC9* was first reported in relation to autosomal recessive Joubert Syndrome 30 in 2017 (PMID:28625504). Joubert syndrome is a rare genetic condition characterized by abnormal brain development that includes the absence or underdevelopment of the cerebellar vermis and a malformed brain stem. Seventeen variants (missense, nonsense, frameshift, splice site) reported in thirteen probands in seven publications (PMIDs: 28625504, 29159890, 35186037, 36584995, 36580738, 30712878, 32304219) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) was reached. This gene-disease association is also supported by a knockout zebrafish model, functional alteration data, and expression studies (PMIDs: 28625504, 32453716). In summary, *ARMC9* is “Definitively” associated with and defined as an autosomal recessive Ciliopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Kidney Cystic and Ciliopathy GCEP on the meeting date 6/28/2023 (SOP Version 9).

Joubert syndrome 30STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033308

Submitter: PanelApp Australia

Joubert syndrome 30STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033308

Submitter: Labcorp Genetics (formerly Invitae)

Joubert syndrome 30DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0033308

Submitter: G2P

Joubert syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018772

Submitter: Orphanet

Clinical Genomic Database (CGD)

Joubert syndrome 30AR

Manifestation: Endocrine; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Endocrine

Rationale: The condition has been described as involving panhypopituitarism, and awareness may allow early diagnosis and medical management (eg, with hormone replacement therapy)

Refs: 28625504

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARMC9 variants in ClinVar

11 Conditions Cataloged

not providedTotal: 656

not specifiedTotal: 94

Inborn genetic diseasesTotal: 90

ARMC9-related disorderTotal: 45

Joubert syndrome 30Total: 36

ARMC9-related Joubert syndromeTotal: 11

Joubert syndromeTotal: 9

Dandy-Walker syndromeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001352754.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	8 clinvar	149 clinvar	3 clinvar	161
missense		6 clinvar	309 clinvar	24 clinvar	6 clinvar	345
nonsense	5 clinvar	7 clinvar	2 clinvar			14
start loss						0
frameshift	8 clinvar	9 clinvar	4 clinvar		1 clinvar	22
splice donor/acceptor (+/-2bp)	3 clinvar	23 clinvar	11 clinvar			37
Total	16	46	334	173	10	579

Highest pathogenic variant AF is 0.00007187255

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 92 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001352754.2	RefSeq	NP_001339683.2	24	MANE Select
ENST00000611582.5	Ensembl	ENSP00000484804.1	24	MANE Select
NM_001271466.4	RefSeq	NP_001258395.2	24	Standard
NM_001291656.2	RefSeq	NP_001278585.2	20	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
armc9	Danio rerio	Structure: photoreceptor cell Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

armc9

Danio rerio

Structure: photoreceptor cell

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cilium assembly

Cellular Component

cytoplasm
ciliary basal body
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000349938
Coding exons: 20
Length: 176289
Individuals with no LoFs: 125663
Homozygous LoFs: 0
Heterozygous LoFs: 85
Defined: 125748
p: 0.000338

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.851	333	380	0.877	0.0000216	4355
Missense (PolyPhen)		106	139.74	0.75855		1576
Synonymous	0.188	150	153	0.981	0.00000912	1254
Loss of Function	1.29	30	38.6	0.776	0.00000182	483

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00035	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00049	0.00049	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00053	0.00038	rare
South Asian	0.00046	0.00042	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for ciliogenesis. {ECO:0000250|UniProtKB:E7F187}.;
Disease: DISEASE: Joubert syndrome 30 (JBTS30) [MIM:617622]: A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS30 inheritance is autosomal recessive. {ECO:0000269|PubMed:28625504}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.243

Intolerance Scores

LoFtool: 0.927
RVIS EVS: 0.25
RVIS percentile EVS: 69.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.380

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium