FAM149B1

protein-coding

family with sequence similarity 149 member B1

Gene summary

Involved in cilium assembly and protein localization to cilium. Predicted to be located in cilium. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

KIAA0974

MANE transcript

NM_173348.2

Inheritance

ClinVar variants

P:15U:101B:26

Top phenotype

Joubert syndrome 36

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr10:73,168,119-73,244,504

External References & Databases

Ensembl (ENSG00000138286)

Transcript & Mutation Effects

hg38 • Region Span ~76.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Joubert syndrome 36STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032902

Submitter: Labcorp Genetics (formerly Invitae)

Joubert syndrome 36STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032902

Submitter: G2P

Joubert syndrome 36MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032902

Submitter: ClinGen

The *FAM149B1* (Family with sequence similarity 149 member B1) gene is located at chromosome 10 at 10q22.2. The encoded protein is involved in the localization of proteins to the cilium and cilium assembly, and is required for normal SHH/smoothened signaling and proper development. *FAM149B1* was first reported in connection with autosomal recessive Joubert syndrome 36 in 2019 (Shaheen et al., 2019 PMID:30905400). Patients typically present with partial or complete agenesis of the cerebellar vermis, molar tooth sign, global developmental delay, ocular movement abnormalities, and mesoaxial polydactyly. Three variants (2 frameshift, 1 nonsense) reported in three probands across two publications were included in this curation (PMIDs: 34828254, 30905400). The mechanism of disease is predicted to be loss of function. This gene-disease pair is also supported by experimental evidence including protein interaction and functional alteration in patient cells (PMIDs: 30905400,35609210). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification is approved by the ClinGen Syndromic Disorders GCEP on the meeting date April 18, 2025 (SOP v11).

Joubert syndrome 36MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032902

Submitter: Ambry Genetics

orofaciodigital syndrome type 6SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010176

Submitter: Orphanet

Joubert syndrome 36LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032902

Submitter: Ambry Genetics

Joubert syndrome 36STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032902

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Joubert syndrome 36AR

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30905400

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FAM149B1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 98

not providedTotal: 27

Joubert syndrome 36Total: 16

FAM149B1-related disorderTotal: 9

Fetal anomalies with a likely genetic causeTotal: 1

Joubert syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173348.2. 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			3 clinvar	17 clinvar		20
missense			87 clinvar	9 clinvar		96
nonsense	2 clinvar	4 clinvar	1 clinvar			7
start loss			2 clinvar			2
frameshift	2 clinvar	6 clinvar	6 clinvar			14
splice donor/acceptor (+/-2bp)	1 clinvar		2 clinvar			3
Total	5	10	101	26	0	142

Highest pathogenic variant AF is 0.00003737118

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173348.2	RefSeq	NP_775483.1	14	MANE Select
ENST00000242505.11	Ensembl	ENSP00000242505.6	14	MANE Select
ENST00000372955.7	Ensembl	ENSP00000362046.3	10	Standard
ENST00000445951.5	Ensembl	ENSP00000402293.1	8	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000242505
Coding exons: 14
Length: 76339
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.56	223	299	0.746	0.0000154	3762
Missense (PolyPhen)		71	97.535	0.72795		1255
Synonymous	0.937	100	113	0.888	0.00000632	1145
Loss of Function	1.34	24	32.2	0.746	0.00000199	382

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

RVIS EVS: 0.73
RVIS percentile EVS: 85.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00767

Gene Damage Prediction

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