FAM149B1

Summary

FAM149B1 (family with sequence similarity 149 member B1, HGNC:29162) is a protein-coding gene on chromosome 10q22.2, encoding Primary cilium assembly protein FAM149B1 (Q96BN6). Involved in the localization of proteins to the cilium and cilium assembly.

Involved in cilium assembly and protein localization to cilium. Predicted to be located in cilium. Implicated in Joubert syndrome.

Source: NCBI Gene 317662 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Joubert syndrome 36 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 82 total — 3 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 62
• MANE Select transcript: NM_173348

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29162
Approved symbol	FAM149B1
Name	family with sequence similarity 149 member B1
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138286
Ensembl biotype	protein_coding
OMIM	618413
Entrez	317662

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000242505, ENST00000372955, ENST00000445951, ENST00000466261, ENST00000468462, ENST00000470798, ENST00000475829, ENST00000607940, ENST00000875781, ENST00000875782, ENST00000927205, ENST00000927206, ENST00000959964, ENST00000959965

RefSeq mRNA: 1 — MANE Select: NM_173348 NM_173348

CCDS: CCDS44435

Canonical transcript exons

ENST00000242505 — 14 exons

Exon	Start	End
ENSE00000987077	73210251	73210438
ENSE00001227807	73235193	73235318
ENSE00001686508	73208619	73208786
ENSE00001767567	73177846	73177975
ENSE00001786916	73193477	73193593
ENSE00001799629	73192556	73192698
ENSE00001801631	73174687	73174791
ENSE00001874014	73240946	73244504
ENSE00001923474	73168119	73168386
ENSE00003466810	73232939	73233163
ENSE00003525533	73234817	73234940
ENSE00003692764	73239312	73239384
ENSE00003710655	73230422	73230525
ENSE00003710771	73228060	73228184

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 91.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.9446 / max 35.3982, expressed in 1202 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105522	1.9446	1202

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	91.83	gold quality
ventricular zone	UBERON:0003053	91.52	gold quality
calcaneal tendon	UBERON:0003701	90.18	gold quality
anterior cingulate cortex	UBERON:0009835	89.83	gold quality
left ovary	UBERON:0002119	89.77	gold quality
cingulate cortex	UBERON:0003027	89.69	gold quality
ganglionic eminence	UBERON:0004023	89.63	gold quality
right testis	UBERON:0004534	89.62	gold quality
left testis	UBERON:0004533	89.58	gold quality
spinal cord	UBERON:0002240	89.42	gold quality
amygdala	UBERON:0001876	89.39	gold quality
right ovary	UBERON:0002118	89.36	gold quality
sperm	CL:0000019	88.96	gold quality
right frontal lobe	UBERON:0002810	88.69	gold quality
metanephros cortex	UBERON:0010533	88.38	gold quality
right uterine tube	UBERON:0001302	88.35	gold quality
adrenal tissue	UBERON:0018303	88.10	gold quality
prefrontal cortex	UBERON:0000451	87.98	gold quality
endocervix	UBERON:0000458	87.88	gold quality
stromal cell of endometrium	CL:0002255	87.84	gold quality
testis	UBERON:0000473	87.83	gold quality
nerve	UBERON:0001021	87.79	gold quality
tibial nerve	UBERON:0001323	87.79	gold quality
gall bladder	UBERON:0002110	87.74	gold quality
body of pancreas	UBERON:0001150	87.69	gold quality
caudate nucleus	UBERON:0001873	87.69	gold quality
body of uterus	UBERON:0009853	87.46	gold quality
right adrenal gland	UBERON:0001233	87.42	gold quality
nucleus accumbens	UBERON:0001882	87.32	gold quality
lower esophagus mucosa	UBERON:0035834	87.31	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting FAM149B1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-657	99.48	66.02	848
HSA-MIR-4728-3P	99.47	68.94	981

Literature-anchored findings (GeneRIF, showing 3)

• FAM149B1 is required for normal ciliary biology and its deficiency results in a range of ciliopathy phenotypes in humans along the spectrum of Joubert syndrome (PMID:30905400)
• Expanding the Phenotype of the FAM149B1-Related Ciliopathy and Identification of Three Neurogenetic Disorders in a Single Family. (PMID:34828254)
• BROMI/TBC1D32 together with CCRK/CDK20 and FAM149B1/JBTS36 contributes to intraflagellar transport turnaround involving ICK/CILK1. (PMID:35609210)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam149b1	ENSDARG00000061215
mus_musculus	Fam149b	ENSMUSG00000039599
rattus_norvegicus	Fam149b1	ENSRNOG00000006554

Paralogs (1): FAM149A (ENSG00000109794)

Protein

Protein identifiers

Primary cilium assembly protein FAM149B1 — Q96BN6 (reviewed: Q96BN6)

All UniProt accessions (4): Q96BN6, H0Y607, H7BY93, V9GYM5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the localization of proteins to the cilium and cilium assembly. Indirectly regulates the signaling functions of the cilium, being required for normal SHH/smoothened signaling and proper development.

Subunit / interactions. Interacts with TBC1D32; may play a role in cilium assembly.

Subcellular location. Cell projection. Cilium.

Disease relevance. Joubert syndrome 36 (JBTS36) [MIM:618763] 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. JBTS36 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the FAM149 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96BN6-1	1	yes
Q96BN6-2	2

RefSeq proteins (1): NP_775483* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022194	DUF3719	Domain
IPR039630	FAM149	Family

Pfam: PF12516

UniProt features (12 total): region of interest 4, compositionally biased region 3, sequence variant 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BN6-F1	52.50	0.05

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 230 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELL_PROJECTION_ORGANIZATION, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, MCCLUNG_DELTA_FOSB_TARGETS_8WK, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_CILIUM, KIM_WT1_TARGETS_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, PDGF_ERK_DN.V1_UP, PDGF_UP.V1_UP

GO Biological Process (3): cilium assembly (GO:0060271), protein localization to cilium (GO:0061512), cell projection organization (GO:0030030)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
protein localization to organelle	1
cellular component organization	1
binding	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

890 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM149B1	DNAJC9	Q8WXX5	965
FAM149B1	DNAJB4	Q9UDY4	550
FAM149B1	E5RHQ9	E5RHQ9	479
FAM149B1	EPCIP	Q9NYP8	471
FAM149B1	TMEM260	Q9NX78	451
FAM149B1	FAM241B	Q96D05	448
FAM149B1	C1orf159	Q96HA4	426
FAM149B1	OOSP2	Q86WS3	409
FAM149B1	CPLANE1	Q9H799	405
FAM149B1	PTCD2	Q8WV60	375
FAM149B1	PLPPR2	Q96GM1	370
FAM149B1	CEP95	Q96GE4	356
FAM149B1	NHEJ1	Q9H9Q4	355
FAM149B1	ALKBH6	Q3KRA9	348
FAM149B1	TBC1D32	Q96NH3	348

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CFAP20	SFSWAP	psi-mi:“MI:0914”(association)	0.620
FAM149B1	TBC1D32	psi-mi:“MI:0915”(physical association)	0.400
FAM149B1	NPW	psi-mi:“MI:0915”(physical association)	0.400
TESC	FAM149B1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): TBC1D32 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), FAM149B1 (Affinity Capture-MS), FAM149B1 (Affinity Capture-MS), FAM149B1 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), NPW (Affinity Capture-MS), FAM149B1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1L8ER70, A1L253, A2AHC3, A5WUN7, B1AZP2, D4AEC2, O14490, P28290, P62024, P97836, P97839, Q148W8, Q14CH0, Q2KI52, Q2M3X8, Q3ZBW7, Q4KM62, Q4R2Y2, Q4R707, Q52KF3, Q5PQL8, Q5R3Z9, Q5RD34, Q5RJX2, Q5VUB5, Q5VZP5, Q5XII9, Q6GLU8, Q6NSV7, Q6P995, Q6PEI3, Q6RFY2, Q7T3E8, Q8BJ42, Q8BYK5, Q8C1B1, Q922B9, Q95X94, Q96BN6, Q96KR7

Diamond homologs: A0JNF3, A1L253, Q5PQL8, Q6NSV7, Q96BN6, A5PLN7, Q8CFV2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

82 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	60
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
3237515	NM_173348.2(FAM149B1):c.1127+1G>A	Pathogenic
4291085	NM_173348.2(FAM149B1):c.574dup (p.Ser192fs)	Pathogenic
810830	NM_173348.2(FAM149B1):c.439C>T (p.Gln147Ter)	Pathogenic
3597261	NM_173348.2(FAM149B1):c.898+1del	Likely pathogenic
3911341	NM_173348.2(FAM149B1):c.822_823del (p.Val274_Phe275insTer)	Likely pathogenic
4291084	NM_173348.2(FAM149B1):c.279T>A (p.Tyr93Ter)	Likely pathogenic
810829	NM_173348.2(FAM149B1):c.356_357del (p.Lys119fs)	Likely pathogenic

SpliceAI

2656 predictions. Top by Δscore:

Variant	Effect	Δscore
10:73168382:GAGCT:G	donor_gain	1.0000
10:73168384:GCT:G	donor_gain	1.0000
10:73168387:G:GG	donor_gain	1.0000
10:73174683:ACAG:A	acceptor_gain	1.0000
10:73174684:CAGGA:C	acceptor_loss	1.0000
10:73174685:A:AG	acceptor_gain	1.0000
10:73174685:A:T	acceptor_loss	1.0000
10:73174685:AG:A	acceptor_gain	1.0000
10:73174686:G:GA	acceptor_loss	1.0000
10:73174686:G:GG	acceptor_gain	1.0000
10:73174686:GG:G	acceptor_gain	1.0000
10:73174686:GGAAA:G	acceptor_gain	1.0000
10:73174789:AAGGT:A	donor_loss	1.0000
10:73174790:AGGT:A	donor_loss	1.0000
10:73174791:GGTAA:G	donor_loss	1.0000
10:73174792:G:GC	donor_loss	1.0000
10:73177831:A:AG	acceptor_gain	1.0000
10:73177831:AAATT:A	acceptor_gain	1.0000
10:73177832:A:G	acceptor_gain	1.0000
10:73177845:GCAA:G	acceptor_gain	1.0000
10:73177947:G:GT	donor_gain	1.0000
10:73177974:GT:G	donor_gain	1.0000
10:73177976:G:GG	donor_gain	1.0000
10:73192553:TAGG:T	acceptor_loss	1.0000
10:73192554:A:AT	acceptor_loss	1.0000
10:73192695:TCAG:T	donor_loss	1.0000
10:73192697:AG:A	donor_loss	1.0000
10:73192698:GGTA:G	donor_loss	1.0000
10:73192699:G:C	donor_loss	1.0000
10:73207936:GAA:G	donor_gain	1.0000

AlphaMissense

3783 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:73192673:T:A	W134R	0.985
10:73192673:T:C	W134R	0.985
10:73192675:G:C	W134C	0.982
10:73192675:G:T	W134C	0.982
10:73192685:T:C	F138L	0.980
10:73192687:T:A	F138L	0.980
10:73192687:T:G	F138L	0.980
10:73210375:T:A	W279R	0.979
10:73210375:T:C	W279R	0.979
10:73210363:T:C	F275L	0.970
10:73210365:T:A	F275L	0.970
10:73210365:T:G	F275L	0.970
10:73193477:G:C	R142S	0.967
10:73193477:G:T	R142S	0.967
10:73192674:G:C	W134S	0.954
10:73192617:T:C	L115S	0.953
10:73193485:G:T	G145V	0.952
10:73192614:T:C	L114P	0.944
10:73193479:T:C	I143T	0.940
10:73208632:G:A	G186R	0.940
10:73208632:G:C	G186R	0.940
10:73208768:C:A	A231E	0.938
10:73192695:T:C	L141P	0.936
10:73192698:G:C	R142T	0.936
10:73210377:G:C	W279C	0.936
10:73210377:G:T	W279C	0.936
10:73208633:G:A	G186E	0.928
10:73208765:T:C	L230P	0.928
10:73193484:G:C	G145R	0.927
10:73208761:T:G	Y229D	0.923

dbSNP variants (sampled 300 via entrez): RS1000063595 (10:73237556 A>G), RS1000066286 (10:73240814 A>C,T), RS1000070960 (10:73199583 C>A,G), RS1000073724 (10:73193123 G>A), RS1000124413 (10:73232622 A>C,G), RS1000168196 (10:73244053 C>A,T), RS1000170906 (10:73215226 G>A,T), RS1000187739 (10:73202737 C>G), RS1000283593 (10:73207717 A>G), RS1000314785 (10:73223281 T>G), RS1000328378 (10:73212275 G>T), RS1000510802 (10:73213129 G>A), RS1000533333 (10:73199365 C>A), RS1000608063 (10:73171219 G>T), RS1000626157 (10:73184667 A>G)

Disease associations

OMIM: gene MIM:618413 | disease phenotypes: MIM:618763, MIM:213300

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 36	Strong	Autosomal recessive
orofaciodigital syndrome type 6	Supportive	Autosomal recessive

Mondo (3): Joubert syndrome 36 (MONDO:0032902), Joubert syndrome (MONDO:0018772), orofaciodigital syndrome type 6 (MONDO:0010176)

Orphanet (1): Isolated Joubert syndrome (Orphanet:475)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000104	Renal agenesis
HP:0000175	Cleft palate
HP:0000180	Lobulated tongue
HP:0000190	Abnormal oral frenulum morphology
HP:0000194	Open mouth
HP:0000199	Tongue nodules
HP:0000218	High palate
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000768	Pectus carinatum
HP:0001156	Brachydactyly
HP:0001159	Syndactyly
HP:0001161	Hand polydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536531	Orofaciodigital syndrome 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
methylparaben	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	increases expression	1
Air Pollutants	decreases expression	1
Arsenic	increases methylation	1
Benzo(a)pyrene	decreases expression	1
Carbamazepine	affects expression	1
Coumestrol	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	decreases methylation	1
Ribonucleotides	affects binding	1
Silicon Dioxide	decreases expression	1
Valproic Acid	decreases expression	1
Asbestos, Crocidolite	decreases expression	1

Clinical trials (associated diseases)

3 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)