TBC1D32

Summary

TBC1D32 (TBC1 domain family member 32, HGNC:21485) is a protein-coding gene on chromosome 6q22.31, encoding Protein broad-minded (Q96NH3). Required for high-level Shh responses in the developing neural tube.

This gene encodes a TBC-domain containing protein. Studies of a similar protein in mouse and zebrafish suggest that the encoded protein is involved in sonic hedgehog signaling, and that it interacts with and stabilizes cell cycle-related kinase. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 221322 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 365 total — 21 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 117
• MANE Select transcript: NM_152730

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21485
Approved symbol	TBC1D32
Name	TBC1 domain family member 32
Location	6q22.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30899, dJ310J6.1, FLJ34235, bA57L9.1, BROMI
Ensembl gene	ENSG00000146350
Ensembl biotype	protein_coding
OMIM	615867
Entrez	221322

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000275159, ENST00000368464, ENST00000398197, ENST00000398212, ENST00000422369, ENST00000464622, ENST00000509492, ENST00000519972, ENST00000523345, ENST00000860462, ENST00000860463, ENST00000923863, ENST00000923864, ENST00000923865, ENST00000923866, ENST00000963966, ENST00000963967, ENST00000963968, ENST00000963969

RefSeq mRNA: 3 — MANE Select: NM_152730 NM_001367759, NM_001367760, NM_152730

CCDS: CCDS43501, CCDS93996

Canonical transcript exons

ENST00000398212 — 32 exons

Exon	Start	End
ENSE00001447185	121317495	121317672
ENSE00001706723	121334276	121334480
ENSE00002102887	121321633	121321794
ENSE00003462939	121160948	121161056
ENSE00003469172	121283818	121283910
ENSE00003492974	121079494	121080890
ENSE00003497949	121112505	121112659
ENSE00003507344	121299446	121299505
ENSE00003512102	121223236	121223352
ENSE00003519854	121126378	121126461
ENSE00003530636	121090853	121091041
ENSE00003531514	121256084	121256285
ENSE00003554516	121255328	121255410
ENSE00003571398	121205075	121205163
ENSE00003585616	121160010	121160103
ENSE00003594622	121292053	121292193
ENSE00003600184	121304522	121304625
ENSE00003601514	121281544	121281686
ENSE00003607319	121279121	121279245
ENSE00003608414	121131627	121131752
ENSE00003611139	121113062	121113177
ENSE00003613145	121239070	121239188
ENSE00003613955	121304755	121304833
ENSE00003614096	121241465	121241552
ENSE00003624037	121310779	121310847
ENSE00003628450	121294570	121294660
ENSE00003634104	121242201	121242339
ENSE00003654715	121303617	121303761
ENSE00003660730	121106023	121106163
ENSE00003660847	121307976	121308101
ENSE00003666888	121115172	121115241
ENSE00003668218	121304365	121304426

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 87.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8394 / max 201.7010, expressed in 1498 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75334	4.7483	1350
75335	1.8846	891
75333	0.2064	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.84	gold quality
adrenal tissue	UBERON:0018303	85.71	gold quality
calcaneal tendon	UBERON:0003701	83.86	gold quality
sperm	CL:0000019	81.93	gold quality
cortical plate	UBERON:0005343	80.06	gold quality
adenohypophysis	UBERON:0002196	79.56	gold quality
sural nerve	UBERON:0015488	79.24	gold quality
pituitary gland	UBERON:0000007	78.94	gold quality
left testis	UBERON:0004533	78.41	gold quality
ventricular zone	UBERON:0003053	78.19	gold quality
testis	UBERON:0000473	78.14	gold quality
ganglionic eminence	UBERON:0004023	78.01	gold quality
embryo	UBERON:0000922	78.00	gold quality
right testis	UBERON:0004534	77.88	gold quality
skin of leg	UBERON:0001511	77.37	gold quality
tibia	UBERON:0000979	76.79	gold quality
right uterine tube	UBERON:0001302	76.68	gold quality
skin of abdomen	UBERON:0001416	76.66	gold quality
right adrenal gland cortex	UBERON:0035827	76.60	gold quality
zone of skin	UBERON:0000014	75.98	gold quality
epithelial cell of pancreas	CL:0000083	75.63	silver quality
right adrenal gland	UBERON:0001233	75.50	gold quality
ectocervix	UBERON:0012249	75.46	gold quality
oocyte	CL:0000023	75.45	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.41	gold quality
gall bladder	UBERON:0002110	75.27	gold quality
tibial nerve	UBERON:0001323	75.04	gold quality
stromal cell of endometrium	CL:0002255	74.85	gold quality
left ovary	UBERON:0002119	74.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6058	no	468.86
E-GEOD-110499	no	43.45
E-ANND-3	no	5.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting TBC1D32, 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-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-380-3P	99.89	70.18	1978
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463

Literature-anchored findings (GeneRIF, showing 6)

• Studies in mouse and zebrafish implicate that TBC1D32 is involved in sonic hedgehog signaling. (PMID:20159594)
• study identified 2 cases with a severe ciliopathy phenotype consistent with oro-facio-digital syndrome type IX; the autozygome of each index harbored a single truncating variant and the affected genes (SCLT1 and TBC1D32/C6orf170) have roles in centrosomal biology and ciliogenesis; findings suggest a role of SCLT1 and TBC1D32 in ciliopathy pathogenesis (PMID:24285566)
• Loss-of-Function Variants in TBC1D32 Underlie Syndromic Hypopituitarism. (PMID:32060556)
• Confirming TBC1D32-related ciliopathy in humans. (PMID:32573025)
• BROMI/TBC1D32 together with CCRK/CDK20 and FAM149B1/JBTS36 contributes to intraflagellar transport turnaround involving ICK/CILK1. (PMID:35609210)
• TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa. (PMID:37768732)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d32	ENSDARG00000041734
mus_musculus	Tbc1d32	ENSMUSG00000038122
rattus_norvegicus	Tbc1d32	ENSRNOG00000000802
caenorhabditis_elegans	T01G9.2	WBGENE00011344

Paralogs (1): PHAF1 (ENSG00000125149)

Protein

Protein identifiers

Protein broad-minded — Q96NH3 (reviewed: Q96NH3)

Alternative names: TBC1 domain family member 32

All UniProt accessions (3): Q96NH3, A2A304, H0YBP0

UniProt curated annotations — full annotation on UniProt →

Function. Required for high-level Shh responses in the developing neural tube. Together with CDK20, controls the structure of the primary cilium by coordinating assembly of the ciliary membrane and axoneme, allowing GLI2 to be properly activated in response to Shh signaling.

Subunit / interactions. Interacts with CDK20, which promotes CDK20 stability and function. Interacts with FAM149B1; may play a role in cilium assembly.

Subcellular location. Cytoplasm. Cell projection. Cilium.

Disease relevance. Orofaciodigital syndrome 9 (OFD9) [MIM:258865] A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD9 is an autosomal recessive form characterized by a variable phenotype. Clinical features are midline defects, including abnormal pituitary development that results in variable pituitary hormone deficiencies, facial dysmorphic features including frontal bossing and hypertelorism, and variable eye defects including microphthalmia, coloboma, and retinal dystrophy. Affected individuals manifest variable psychomotor development. The disease is caused by variants affecting the gene represented in this entry. Retinitis pigmentosa 100 (RP100) [MIM:621280] A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP100 is an autosomal recessive form characterized by the onset of night blindness in childhood or young adulthood, followed by progressive visual field constriction. The disease is caused by variants affecting the gene represented in this entry. Alsahan-Harris syndrome (ALHAS) [MIM:621307] An autosomal recessive syndrome characterized by severe, prenatal features that include holoprosencephaly, anencephaly, ocular defects such as microphthalmia, anophthalmia and cyclopia, and digital anomalies. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96NH3-1	1	yes
Q96NH3-4	2
Q96NH3-5	3

RefSeq proteins (3): NP_001354688, NP_001354689, NP_689943* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032735	BROMI_M	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR039156	PHAF1/BROMI	Family
IPR055391	BROMI_N	Domain
IPR055392	BROMI_C	Domain

Pfam: PF14961, PF23431, PF23440

UniProt features (22 total): sequence variant 12, sequence conflict 3, splice variant 3, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NH3-F1	80.84	0.36

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 125 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, TGCGCANK_UNKNOWN, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_CILIUM_ORGANIZATION, GOBP_APPENDAGE_DEVELOPMENT, GOBP_ORGANELLE_ASSEMBLY, ATF3_Q6, CREB_Q2_01, ATF4_Q2, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (17): kidney development (GO:0001822), lens development in camera-type eye (GO:0002088), retinal pigment epithelium development (GO:0003406), determination of left/right symmetry (GO:0007368), heart development (GO:0007507), embryonic digit morphogenesis (GO:0042733), roof of mouth development (GO:0060021), smoothened signaling pathway involved in dorsal/ventral neural tube patterning (GO:0060831), protein localization to cilium (GO:0061512), non-motile cilium assembly (GO:1905515), smoothened signaling pathway (GO:0007224), neural tube patterning (GO:0021532), dorsal/ventral neural tube patterning (GO:0021904), neural tube development (GO:0021915), camera-type eye development (GO:0043010), retina development in camera-type eye (GO:0060041), cilium assembly (GO:0060271)

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

GO Cellular Component (3): cytoplasm (GO:0005737), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
animal organ development	2
camera-type eye development	2
epithelium development	2
cellular anatomical structure	2
renal system development	1
retina development in camera-type eye	1
determination of bilateral symmetry	1
left/right pattern formation	1
circulatory system development	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
smoothened signaling pathway	1
dorsal/ventral neural tube patterning	1
protein localization to organelle	1
cilium assembly	1
cell surface receptor signaling pathway	1
regionalization	1
neural tube development	1
dorsal/ventral pattern formation	1
neural tube patterning	1
nervous system development	1
tube development	1
chordate embryonic development	1
eye development	1
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
binding	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D32	SCLT1	Q96NL6	715
TBC1D32	DDX59	Q5T1V6	571
TBC1D32	WDPCP	O95876	563
TBC1D32	CFAP20	Q9Y6A4	528
TBC1D32	UEVLD	Q8IX04	528
TBC1D32	OFD1	O75665	507
TBC1D32	ANKS6	Q68DC2	476
TBC1D32	CPLANE2	Q9BU20	464
TBC1D32	MPP7	Q5T2T1	455
TBC1D32	TMEM216	Q9P0N5	438
TBC1D32	GRTP1	Q5TC63	438
TBC1D32	CDC16	Q13042	437
TBC1D32	QRICH1	Q2TAL8	406
TBC1D32	TCTN3	Q6NUS6	403
TBC1D32	TMEM67	Q5HYA8	399

IntAct

24 interactions, top by confidence:

A	B	Type	Score
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820
CFAP20	SFSWAP	psi-mi:“MI:0914”(association)	0.620
SLC9A6	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
FOXJ1	PEX14	psi-mi:“MI:0914”(association)	0.530
SLC9A6	IFNGR1	psi-mi:“MI:0914”(association)	0.530
CFAP20	KPNA4	psi-mi:“MI:0914”(association)	0.510
TBC1D32	H1-5	psi-mi:“MI:0915”(physical association)	0.400
FAM149B1	TBC1D32	psi-mi:“MI:0915”(physical association)	0.400
FOXJ1	ACSL4	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
SFSWAP	U2SURP	psi-mi:“MI:0914”(association)	0.350
CDK7	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
CFAP20	RABEPK	psi-mi:“MI:0914”(association)	0.350
SLC9A6	GOLIM4	psi-mi:“MI:0914”(association)	0.350
TBC1D32	HDAC1	psi-mi:“MI:0915”(physical association)	0.000
RFX3	TBC1D32	psi-mi:“MI:0915”(physical association)	0.000
CFAP20	TBC1D32	psi-mi:“MI:0915”(physical association)	0.000
TBC1D32	XYLT2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (105): TBC1D32 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), TBC1D32 (Affinity Capture-MS), HDAC1 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), TBC1D32 (Proximity Label-MS), TBC1D32 (Proximity Label-MS), TBC1D32 (Affinity Capture-MS)

ESM2 similar proteins: A1A535, A2AIV2, A2RRP1, A8XSV3, D3YVL2, F1QJX5, F1QN74, Q09263, Q0KK59, Q14D04, Q19317, Q3UHQ6, Q3URV1, Q3V129, Q571H0, Q5JWR5, Q5PQS3, Q5RHR6, Q5SPP5, Q5TYW4, Q5U430, Q5WNI9, Q5ZLS8, Q61QK6, Q620W3, Q642P2, Q69YN4, Q69ZR2, Q6GN08, Q6TNU3, Q6ZQ18, Q6ZT12, Q7Z3E5, Q86VV8, Q8BL99, Q8GY23, Q8H0T4, Q8IGJ0, Q8K2A7, Q8R4Y8

Diamond homologs: Q3URV1, Q5RHR6, Q96NH3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	6
Uncertain significance	210
Likely benign	63
Benign	38

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1377473	NM_152730.6(TBC1D32):c.283C>T (p.Gln95Ter)	Pathogenic
2054643	NM_152730.6(TBC1D32):c.3107G>A (p.Trp1036Ter)	Pathogenic
2140434	NM_152730.6(TBC1D32):c.434del (p.Lys145fs)	Pathogenic
2957961	NM_152730.6(TBC1D32):c.795_798del (p.Ser266fs)	Pathogenic
3628829	NM_152730.6(TBC1D32):c.2350C>T (p.Arg784Ter)	Pathogenic
4071488	NM_152730.6(TBC1D32):c.317+5G>A	Pathogenic
4071489	TBC1D32, 5-BP DEL, 846TCCTA	Pathogenic
4071490	NM_152730.6(TBC1D32):c.18_27del (p.Ser6fs)	Pathogenic
4071491	NM_152730.6(TBC1D32):c.1141-1G>A	Pathogenic
4071492	NM_152730.6(TBC1D32):c.1267G>T (p.Glu423Ter)	Pathogenic
4071493	TBC1D32, TRP1171CYS	Pathogenic
4071494	D1170Y	Pathogenic
4071495	TBC1D32, IVS9, G-A, -1	Pathogenic
4075386	NM_152730.6(TBC1D32):c.2151del (p.Lys717fs)	Pathogenic
4075388	R734*	Pathogenic
4075389	TBC1D32, IVS, G-T, -1	Pathogenic
4075390	TBC1D32, 1-BP DEL, NT2073	Pathogenic
4075391	TBC1D32, IVS6, G-A, +5	Pathogenic
4075393	R1242*	Pathogenic
4075395	NM_152730.6(TBC1D32):c.3325_3326delAG	Pathogenic
4707686	NM_152730.6(TBC1D32):c.2151dup (p.Leu718fs)	Pathogenic
139613	NM_152730.6(TBC1D32):c.1372+1G>T	Likely pathogenic
2279946	NM_152730.6(TBC1D32):c.2482-2A>G	Likely pathogenic
2632969	NM_152730.6(TBC1D32):c.2545G>T (p.Glu849Ter)	Likely pathogenic
3220914	NM_152730.6(TBC1D32):c.3724C>T (p.Arg1242Ter)	Likely pathogenic
3769638	NM_152730.6(TBC1D32):c.1551del (p.Asn517fs)	Likely pathogenic
4279038	NM_152730.6(TBC1D32):c.1774dup (p.Leu592fs)	Likely pathogenic

SpliceAI

6269 predictions. Top by Δscore:

Variant	Effect	Δscore
6:121106009:C:CA	donor_gain	1.0000
6:121112503:A:AC	donor_gain	1.0000
6:121112504:C:CC	donor_gain	1.0000
6:121112656:CAGA:C	acceptor_gain	1.0000
6:121112660:C:CC	acceptor_gain	1.0000
6:121113051:A:AC	donor_gain	1.0000
6:121113052:A:C	donor_gain	1.0000
6:121115242:C:CC	acceptor_gain	1.0000
6:121115625:T:A	donor_gain	1.0000
6:121115637:T:C	donor_gain	1.0000
6:121128978:C:A	donor_gain	1.0000
6:121131753:C:CC	acceptor_gain	1.0000
6:121131759:A:T	acceptor_gain	1.0000
6:121160099:TCACT:T	acceptor_gain	1.0000
6:121160100:CACT:C	acceptor_gain	1.0000
6:121160100:CACTC:C	acceptor_gain	1.0000
6:121160101:ACTCT:A	acceptor_loss	1.0000
6:121160102:CT:C	acceptor_gain	1.0000
6:121160103:TC:T	acceptor_loss	1.0000
6:121160104:C:CC	acceptor_gain	1.0000
6:121223229:GACT:G	donor_loss	1.0000
6:121223230:ACTT:A	donor_loss	1.0000
6:121223231:CT:C	donor_loss	1.0000
6:121223232:TT:T	donor_loss	1.0000
6:121223233:TAC:T	donor_loss	1.0000
6:121223234:A:AC	donor_gain	1.0000
6:121223234:A:T	donor_loss	1.0000
6:121223235:C:CA	donor_gain	1.0000
6:121223235:CA:C	donor_gain	1.0000
6:121223235:CAATA:C	donor_gain	1.0000

AlphaMissense

8309 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:121303622:A:G	W359R	0.995
6:121303622:A:T	W359R	0.995
6:121303634:A:G	W355R	0.995
6:121303634:A:T	W355R	0.995
6:121091029:A:G	W1160R	0.994
6:121091029:A:T	W1160R	0.994
6:121321774:A:G	L59P	0.990
6:121334281:A:C	F50L	0.989
6:121334281:A:T	F50L	0.989
6:121334283:A:G	F50L	0.989
6:121091011:A:G	W1166R	0.988
6:121091011:A:T	W1166R	0.988
6:121299491:G:C	S365R	0.987
6:121299491:G:T	S365R	0.987
6:121299493:T:G	S365R	0.987
6:121304384:A:G	W306R	0.987
6:121304384:A:T	W306R	0.987
6:121161020:A:C	N869K	0.986
6:121161020:A:T	N869K	0.986
6:121080871:A:G	F1225S	0.985
6:121112627:A:G	W1068R	0.985
6:121112627:A:T	W1068R	0.985
6:121161012:A:G	L872P	0.985
6:121112528:A:G	W1101R	0.984
6:121112528:A:T	W1101R	0.984
6:121304419:A:G	L294P	0.984
6:121334282:A:G	F50S	0.984
6:121113172:C:T	G1020D	0.983
6:121239159:A:G	W759R	0.983
6:121239159:A:T	W759R	0.983

dbSNP variants (sampled 300 via entrez): RS1000000895 (6:121120978 T>A,G), RS1000019749 (6:121301359 A>G), RS1000027384 (6:121274231 G>A), RS1000040652 (6:121102045 C>G,T), RS1000056412 (6:121154429 C>T), RS1000057540 (6:121216240 C>T), RS1000062063 (6:121151270 T>C,G), RS1000074139 (6:121209872 T>C), RS1000088797 (6:121326682 T>C), RS1000094775 (6:121149959 A>C,T), RS1000099211 (6:121253190 A>G), RS1000124510 (6:121085843 T>C), RS1000125846 (6:121238969 A>C,G), RS1000144365 (6:121105621 A>T), RS1000178810 (6:121119044 G>A,T)

Disease associations

OMIM: gene MIM:615867 | disease phenotypes: MIM:258865, MIM:621307, MIM:618763, MIM:165550, MIM:621280

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliopathy	Definitive	Autosomal recessive
orofaciodigital syndrome IX	Strong	Autosomal recessive
orofaciodigital syndrome	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
ciliopathy	Definitive	AR

Mondo (9): orofaciodigital syndrome IX (MONDO:0009795), Alsahan-Harris syndrome (MONDO:0979871), hypopituitarism (MONDO:0005152), ciliopathy (MONDO:0005308), Joubert syndrome 36 (MONDO:0032902), isolated optic nerve hypoplasia (MONDO:0008136), retinitis pigmentosa 100 (MONDO:0979574), microcephaly (MONDO:0001149), orofaciodigital syndrome (MONDO:0015375)

Orphanet (4): Orofaciodigital syndrome type 9 (Orphanet:141007), Ciliopathy (Orphanet:363250), Isolated optic nerve hypoplasia (Orphanet:637061), OBSOLETE: Isolated optic nerve hypoplasia/aplasia (Orphanet:137902)

HPO phenotypes

117 total (30 of 117 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000089	Renal hypoplasia
HP:0000161	Median cleft upper lip
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000191	Accessory oral frenulum
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000448	Prominent nose
HP:0000453	Choanal atresia
HP:0000455	Broad nasal tip
HP:0000456	Bifid nasal tip
HP:0000463	Anteverted nares
HP:0000480	Retinal coloboma
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000506	Telecanthus
HP:0000528	Anophthalmia
HP:0000543	Optic disc pallor
HP:0000568	Microphthalmia
HP:0000589	Coloboma

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000579_50	Cognitive performance	2.000000e-06
GCST002948_1	Peak creatinine levels in vancomycin therapy	1.000000e-07
GCST007656_4	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D007018	Hypopituitarism	C10.228.140.617.738.300; C19.700.482
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009958	Orofaciodigital Syndromes	C05.116.099.370.652; C05.660.207.700; C16.131.077.676; C16.131.260.830.670; C16.131.621.207.700; C16.320.180.830.670; C16.320.714
C557818	Orofaciodigital syndrome 9 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7740004	Toxicity	3	Bisphosphonates	Osteonecrosis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7740004	TBC1D32	3	0.00	1	Bisphosphonates

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	3
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	decreases expression	1
Formaldehyde	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Herbicides	affects methylation, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Picloram	affects methylation, increases abundance	1
Polycyclic Aromatic Hydrocarbons	increases abundance, affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	increases expression	1
1-Butanol	affects cotreatment, decreases expression, increases abundance	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00140413	PHASE4	COMPLETED	Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia
NCT00360074	PHASE4	COMPLETED	Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation
NCT00490191	PHASE4	COMPLETED	Comparison of Two Growth Hormone Dosing Methods in Adults With Growth Hormone Deficiency
NCT00851942	PHASE4	COMPLETED	Determination of Method-specific Normal Cortisol and Adrenal Hormone Responses to the Short Synacthen Test
NCT04897802	PHASE4	COMPLETED	Identification and Clinical Relevance of an Oxytocin Deficient State (GLP1 Study)
NCT04902235	PHASE4	COMPLETED	Identification and Clinical Relevance of an Oxytocin Deficient State (CRH Study)
NCT05188131	PHASE4	COMPLETED	Acute Neuroendocrine Response to Intravenous Infusion of Diclofenac Sodium
NCT05206149	PHASE4	COMPLETED	Stimulation Test With Intranasal Glucagon for Corticotroph, Somatotroph and Antidiuretic Axes
NCT01007071	PHASE3	COMPLETED	Effects of Growth Hormone on Cognition and Cerebral Metabolism in Adults With Growth Hormone Deficiency
NCT06760546	PHASE3	RECRUITING	A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)
NCT00080483	PHASE2	COMPLETED	Testosterone and Growth Hormone for Bone Loss in Men
NCT04121780	PHASE2	RECRUITING	Growth Hormone Replacement Therapy for Retried Professional Football Players
NCT00068224	Not specified	COMPLETED	Clinical and Molecular Investigations Into Ciliopathies
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT01962129	Not specified	UNKNOWN	Clinical and Molecular Characterisation of Orofaciodigital Syndromes and Other Clinical Phenotypes Secondary to Mutations in the OFD1 Gene
NCT00133354	PHASE2/PHASE3	COMPLETED	Arimidex Multicenter Trial in Growth Hormone (GH) Deficient Boys
NCT07568509	EARLY_PHASE1	RECRUITING	Identifying Oxytocin Deficiency in Pediatric Patients With Pituitary Disease
NCT00027430	Not specified	COMPLETED	Androgen Replacement Therapy in Women With Hypopituitarism
NCT00139945	Not specified	COMPLETED	Ghrelin, Growth Hormone and Cortisol Interaction in Growth Hormone Deficient Patients
NCT00462475	Not specified	COMPLETED	Effect of 5 Years of GH Replacement on Atherosclerosis
NCT00504218	Not specified	TERMINATED	Detection and Treatment of Endocrine Abnormalities in Childhood Cancer Survivors and Hematopoietic Stem Cell Transplant Recipients
NCT00507104	Not specified	COMPLETED	Pituitary Functions After Traumatic Brain Injury (TBI) and/or Subarachnoid Hemorrhage (SAH)
NCT00572390	Not specified	COMPLETED	Oestrogen Withdrawal in Hypopituitary Women
NCT00666068	Not specified	COMPLETED	Effects of Corticotropin Releasing Hormone (CRH) on the Sleep in Patients With Hypopituitarism
NCT00962559	Not specified	COMPLETED	Hypopituitarism After Aneurismal Subarachnoid Hemorrhage
NCT01009905	Not specified	COMPLETED	An Observational Study (Registry) Assessing Treatment Outcomes and Safety for Children and Adults Who Are Prescribed Norditropin® (Human Growth Hormone)
NCT01028742	Not specified	COMPLETED	Posttraumatic Hypopituitarism - Incidence, Predictors and Test Validity
NCT01088399	Not specified	COMPLETED	A Prospective Observational Study of Effect of Somatropin on Growth Hormone Deficient Adults
NCT01209416	Not specified	COMPLETED	The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin
NCT01574859	Not specified	COMPLETED	Central Hypothyroidism and Cardiovascular Risk
NCT01666964	Not specified	UNKNOWN	Hormone Deficiency After Brain Injury During Combat
NCT02360046	Not specified	TERMINATED	The Influence of Different Hydrocortisone Replacement Doses on the Partitioning and Flexibility of Ectopic Lipids in Patients With Corticotropic Hypopituitarism
NCT02782208	Not specified	COMPLETED	Lipolytic Effects of GH in Hypopituitary Patients in Vivo
NCT02871986	Not specified	UNKNOWN	Pubertal Induction in Individuals With Hypogonadism
NCT03708523	Not specified	UNKNOWN	Next Day Growth Hormone Predicting Pituitary Function After Adenomectomy
NCT05319301	Not specified	COMPLETED	Identification and Clinical Relevance of an Oxytocin Deficient State (Melatonin Study)
NCT05990491	Not specified	RECRUITING	Pituitary Function After Recovery From Septic Shock Among ICU Survivors
NCT06014398	Not specified	UNKNOWN	Improving Survivorship and Health-related Quality of Life in Patients With Primary Brain Tumours
NCT06326853	Not specified	NOT_YET_RECRUITING	Neuroendocrine Mechanisms in Adiposity: An Integrated Approach to the Characterization of Potential Pharmacological Novel Targets Based on Experimental and Clinical Models
NCT07015645	Not specified	COMPLETED	Long-Term Outcomes of Hypopituitarism Following Gamma Knife Radiosurgery for Pituitary Adenomas