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GeneE
7 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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FAM149B1
family with sequence similarity 149 member B1
Chromosome 10 Β· 10q22.2
NCBI Gene: 317662Ensembl: ENSG00000138286.16HGNC: HGNC:29162UniProt: Q96BN6
12PubMed Papers
21Diseases
0Drugs
10Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcilium assemblyprotein localization to ciliumciliumJoubert syndrome 36neurodegenerative diseaseorofaciodigital syndrome type 6Joubert syndrome with orofaciodigital defect
✦AI Summary

FAM149B1 is a DUF3719-domain-containing protein essential for primary cilium assembly and function 1. The protein regulates cilia architecture by promoting CCRK kinase activity to control the localization and function of MAK kinase, thereby modulating axonemal microtubule stability and ciliary length 1. FAM149B1 also participates in intraflagellar transport (IFT) turnaround at the ciliary tip through direct interactions with BROMI/TBC1D32 and CCRK/CDK20, which together regulate ICK/CILK1 kinase-dependent directional switching of the IFT machinery 2. Disruption of FAM149B1 results in ciliary dysfunction characterized by abnormally elongated cilia, accumulation of IFT machinery at the distal ciliary tip, dysregulated sonic hedgehog signaling, and bulbous ciliary morphology 3. Bi-allelic FAM149B1 mutations cause Joubert syndrome 36, a ciliopathy presenting with neurological features including developmental delay, oculomotor apraxia, hypotonia, and skeletal abnormalities 34. Clinical manifestations expand beyond the classic Joubert phenotype to include variable orofaciodigital features, progressive ophthalmoplegia, ataxia, polydactyly, and corpus callosal dysgenesis 4. FAM149B1 was also identified as a biomarker protein in distinguishing follicular thyroid carcinoma from benign follicular adenoma using proteomics analysis 5, though this association requires validation for clinical significance.

Sources cited
1
FAM149B1 (xbx-4 homolog) regulates cilia length and structure through the CCRK and MAK kinase pathway; mutations in FAM149B1 elongate cilia and cause Joubert syndrome
PMID: 34731674
2
FAM149B1 interacts with BROMI and CCRK to regulate intraflagellar transport turnaround and ciliary homeostasis; deficiency causes abnormally long cilia and IFT machinery accumulation
PMID: 35609210
3
Bi-allelic FAM149B1 mutations cause ciliopathy phenotypes including Joubert syndrome and orofaciodigital syndrome VI with abnormal cilia, dysregulated SHH signaling, and IFT complex accumulation
PMID: 30905400
4
FAM149B1 mutations result in neurological and oculomotor ciliopathy with mild skeletal dysplasia, ataxia, polydactyly, progressive ophthalmoplegia, and olfactory bulb aplasia
PMID: 34828254
5
FAM149B1 identified as a biomarker protein in machine learning models for distinguishing follicular thyroid carcinoma from follicular adenoma
PMID: 40205804
Disease Associationsβ“˜21
Joubert syndrome 36Open Targets
0.73Strong
neurodegenerative diseaseOpen Targets
0.44Moderate
Joubert syndrome with orofaciodigital defectOpen Targets
0.37Weak
orofaciodigital syndrome type 6Open Targets
0.37Weak
syndromic intellectual disabilityOpen Targets
0.37Weak
atrial fibrillationOpen Targets
0.34Weak
Joubert syndromeOpen Targets
0.31Weak
congestive heart failureOpen Targets
0.22Weak
orofaciodigital syndromeOpen Targets
0.18Weak
azoospermiaOpen Targets
0.09Suggestive
alcohol drinkingOpen Targets
0.08Suggestive
Male infertility with spermatogenesis disorder due to single gene mutationOpen Targets
0.07Suggestive
Female infertility due to fertilization defectOpen Targets
0.07Suggestive
Rare genetic female infertilityOpen Targets
0.07Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
spermatogenic failure 3Open Targets
0.06Suggestive
spermatogenic failure 55Open Targets
0.06Suggestive
spermatogenic failure 26Open Targets
0.06Suggestive
spermatogenic failure 31Open Targets
0.06Suggestive
spermatogenic failure 53Open Targets
0.06Suggestive
Joubert syndrome 36UniProt
Pathogenic Variants10
NM_173348.2(FAM149B1):c.574dup (p.Ser192fs)Pathogenic
Joubert syndrome 36
β˜…β˜†β˜†β˜†2025β†’ Residue 192
NM_173348.2(FAM149B1):c.279T>A (p.Tyr93Ter)Likely pathogenic
Joubert syndrome 36
β˜…β˜†β˜†β˜†2025β†’ Residue 93
NM_173348.2(FAM149B1):c.822_823del (p.Val274_Phe275insTer)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 274
NM_173348.2(FAM149B1):c.356_357del (p.Lys119fs)Likely pathogenic
Joubert syndrome 36|Joubert syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 119
NM_173348.2(FAM149B1):c.1402C>T (p.Arg468Ter)Likely pathogenic
Joubert syndrome 36
β˜…β˜†β˜†β˜†2024β†’ Residue 468
NM_173348.2(FAM149B1):c.898+1delLikely pathogenic
Joubert syndrome 36
β˜…β˜†β˜†β˜†2024
NM_173348.2(FAM149B1):c.1127+1G>APathogenic
Joubert syndrome 36|Clear cell carcinoma of kidney
β˜…β˜†β˜†β˜†2024
NM_173348.2(FAM149B1):c.1198C>T (p.Arg400Ter)Pathogenic
Joubert syndrome 36
β˜…β˜†β˜†β˜†2024β†’ Residue 400
NM_173348.2(FAM149B1):c.1183C>T (p.Arg395Ter)Likely pathogenic
Joubert syndrome 36
β˜…β˜†β˜†β˜†2023β†’ Residue 395
NM_173348.2(FAM149B1):c.439C>T (p.Gln147Ter)Pathogenic
Joubert syndrome 36
β˜†β˜†β˜†β˜†2020β†’ Residue 147
View on ClinVar β†—
Related Genes
ASAP1Shared pathway100%DNAJC9Protein interaction97%TBC1D32Protein interaction89%CFAP20Protein interaction83%BBS9Shared pathway67%TTC21BShared pathway50%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
95%
Heart
88%
Brain
79%
Liver
75%
Lung
57%
Gene Interaction Network
Click a node to explore
FAM149B1ASAP1DNAJC9TBC1D32CFAP20BBS9TTC21B
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q96BN6
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.98LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.74 [0.57–0.98]
RankingsWhere FAM149B1 stands among ~20K protein-coding genes
  • #16,441of 20,598
    Most Researched12
  • #2,899of 5,498
    Most Pathogenic Variants10
  • #9,352of 17,882
    Most Constrained (LOEUF)0.98
Genes detectedFAM149B1
Sources retrieved7 papers
Response timeβ€”
πŸ“„ Sources
7β–Ό
1
xbx-4, a homolog of the Joubert syndrome gene FAM149B1, acts via the CCRK and RCK kinase cascade to regulate cilia morphology.
PMID: 34731674
Curr Biol Β· 2021
1.00
2
BROMI/TBC1D32 together with CCRK/CDK20 and FAM149B1/JBTS36 contributes to intraflagellar transport turnaround involving ICK/CILK1.
PMID: 35609210
Mol Biol Cell Β· 2022
0.86
3
Comprehensive Proteomics and Machine Learning Analysis to Distinguish Follicular Adenoma and Follicular Thyroid Carcinoma from Indeterminate Thyroid Nodules.
PMID: 40205804
Endocrinol Metab (Seoul) Β· 2025
0.71
4
Bi-allelic Mutations in FAM149B1 Cause Abnormal Primary Cilium and a Range of Ciliopathy Phenotypes in Humans.
PMID: 30905400
Am J Hum Genet Β· 2019
0.57
5
Expanding the Phenotype of the
PMID: 34828254
Genes (Basel) Β· 2021
0.43