SDCCAG8

Summary

SDCCAG8 (SHH signaling and ciliogenesis regulator SDCCAG8, HGNC:10671) is a protein-coding gene on chromosome 1q43-q44, encoding Serologically defined colon cancer antigen 8 (Q86SQ7). Plays a role in the establishment of cell polarity and epithelial lumen formation.

This gene encodes a centrosome associated protein. This protein may be involved in organizing the centrosome during interphase and mitosis. Mutations in this gene are associated with retinal-renal ciliopathy.

Source: NCBI Gene 10806 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Bardet-Biedl syndrome 16 (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 49
• Clinical variants (ClinVar): 764 total — 44 pathogenic, 44 likely-pathogenic
• Phenotypes (HPO): 119
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_006642

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10671
Approved symbol	SDCCAG8
Name	SHH signaling and ciliogenesis regulator SDCCAG8
Location	1q43-q44
Locus type	gene with protein product
Status	Approved
Aliases	NY-CO-8, CCCAP, SLSN7, NPHP10, BBS16
Ensembl gene	ENSG00000054282
Ensembl biotype	protein_coding
OMIM	613524
Entrez	10806

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 11 protein_coding, 8 protein_coding_CDS_not_defined

ENST00000366541, ENST00000435549, ENST00000463012, ENST00000463042, ENST00000476722, ENST00000482234, ENST00000490065, ENST00000491888, ENST00000493334, ENST00000496361, ENST00000497459, ENST00000884079, ENST00000884080, ENST00000884081, ENST00000884082, ENST00000926803, ENST00000951623, ENST00000951624, ENST00000951625

RefSeq mRNA: 6 — MANE Select: NM_006642 NM_001350246, NM_001350247, NM_001350248, NM_001350249, NM_001350251, NM_006642

CCDS: CCDS31075

Canonical transcript exons

ENST00000366541 — 18 exons

Exon	Start	End
ENSE00001129001	243270105	243270257
ENSE00001315573	243417968	243418076
ENSE00001412181	243330540	243330692
ENSE00001441969	243316755	243316893
ENSE00001649711	243499756	243500091
ENSE00001939110	243256041	243256240
ENSE00003461674	243426427	243426558
ENSE00003484773	243307989	243308177
ENSE00003507928	243270978	243271063
ENSE00003509937	243304713	243304777
ENSE00003522733	243344215	243344331
ENSE00003527889	243286272	243286397
ENSE00003532629	243489014	243489140
ENSE00003545852	243341039	243341173
ENSE00003569907	243274543	243274656
ENSE00003641050	243378721	243378863
ENSE00003642423	243415702	243415829
ENSE00003653350	243293091	243293219

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.9351 / max 307.1147, expressed in 1816 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9410	22.6771	1814
9434	1.0371	237
9433	0.9831	310
9411	0.4405	218
9432	0.3957	192
9420	0.2542	56
9409	0.1005	37
202026	0.0469	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	97.30	gold quality
calcaneal tendon	UBERON:0003701	95.52	gold quality
thyroid gland	UBERON:0002046	93.78	gold quality
bone marrow cell	CL:0002092	93.37	gold quality
left lobe of thyroid gland	UBERON:0001120	93.35	gold quality
right lobe of thyroid gland	UBERON:0001119	93.10	gold quality
sural nerve	UBERON:0015488	92.64	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.56	gold quality
right lung	UBERON:0002167	92.52	gold quality
tonsil	UBERON:0002372	92.36	gold quality
right uterine tube	UBERON:0001302	91.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.95	gold quality
body of pancreas	UBERON:0001150	91.82	gold quality
pancreas	UBERON:0001264	91.72	gold quality
adrenal tissue	UBERON:0018303	91.65	gold quality
skin of leg	UBERON:0001511	91.45	gold quality
ventricular zone	UBERON:0003053	91.37	gold quality
Ammon’s horn	UBERON:0001954	91.36	gold quality
islet of Langerhans	UBERON:0000006	91.33	gold quality
skeletal muscle tissue	UBERON:0001134	91.32	gold quality
lung	UBERON:0002048	91.28	gold quality
gall bladder	UBERON:0002110	91.16	gold quality
zone of skin	UBERON:0000014	91.15	gold quality
substantia nigra	UBERON:0002038	91.13	gold quality
cortical plate	UBERON:0005343	90.94	gold quality
temporal lobe	UBERON:0001871	90.92	gold quality
amygdala	UBERON:0001876	90.88	gold quality
fallopian tube	UBERON:0003889	90.85	gold quality
muscle tissue	UBERON:0002385	90.84	gold quality
bone marrow	UBERON:0002371	90.82	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-124858	yes	107.77
E-ANND-3	yes	19.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting SDCCAG8, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-3664-5P	96.74	66.56	770
HSA-MIR-6879-3P	93.93	64.00	759

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 11)

• Mutation of SDCCAG8 is associated with retinal-renal ciliopathy. (PMID:20835237)
• Intronic variants of SDCCAG8, which are associated with early onset obesity, are associated with reduced weight loss after a 1-year lifestyle intervention in overweight children and adolescents even after adjusting for age, sex, baseline measurement. (PMID:22095114)
• significant associations in schizophrenia to SDCAAG8 and extensive replication of associations reported by the Schizophrenia. (PMID:22614287)
• Our results and prior literature suggest that SDCCAG8 could play an important role in presumed Bardet-Biedl syndrome (BBS) patients affected with severe kidney disease and absent polydactyly. (PMID:22626039)
• Variants in NPHS2, SDCCAG8 and near BMP4 appear to interact with APOL1 to modulate the risk for non-diabetic end stage kidney disease in african americans. (PMID:24157943)
• Results suggest that SDCCAG8 promote the proliferation, migration and invasion of head and neck squamous cell carcinoma (HNSCC) cells. Sdccag8 is a downstream target gene of SOX11 in HNSCC cells. (PMID:30922366)
• Altered gene regulation as a candidate mechanism by which ciliopathy gene SDCCAG8 contributes to schizophrenia and cognitive function. (PMID:31868218)
• Genetic Variants May Play Role in Opioid Dependence. (PMID:32453508)
• A novel splice site mutation in the SDCCAG8 gene in an Iranian family with Bardet-Biedl syndrome. (PMID:32926352)
• Genetic variants of SDCCAG8 and MAGI2 in mitosis-related pathway genes are independent predictors of cutaneous melanoma-specific survival. (PMID:34375487)
• The carboxyl-terminal region of SDCCAG8 comprises a functional module essential for cilia formation as well as organ development and homeostasis. (PMID:35131266)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sdccag8	ENSMUSG00000026504
rattus_norvegicus	Sdccag8	ENSRNOG00000004181

Protein

Protein identifiers

Serologically defined colon cancer antigen 8 — Q86SQ7 (reviewed: Q86SQ7)

Alternative names: Antigen NY-CO-8, Centrosomal colon cancer autoantigen protein

All UniProt accessions (3): A0A0C4DG71, Q86SQ7, S4R323

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the establishment of cell polarity and epithelial lumen formation. Also plays an essential role in ciliogenesis and subsequent Hedgehog signaling pathway that requires the presence of intact primary cilia for pathway activation. Mechanistically, interacts with and mediates RABEP2 centrosomal localization which is critical for ciliogenesis.

Subunit / interactions. Homodimer. Interacts with OFD1; the interaction is direct. Interacts with FAM161A. Interacts with RABEP2, ERC1 and CEP131.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Cilium basal body. Cell junction Cytoplasm.

Tissue specificity. Expressed in thymus, prostate, testis, ovary, small intestine, colon, mucosa, colon and renal cancer tumors.

Disease relevance. Senior-Loken syndrome 7 (SLSN7) [MIM:613615] A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. The disease is caused by variants affecting the gene represented in this entry. Bardet-Biedl syndrome 16 (BBS16) [MIM:615993] A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q86SQ7-1	1, a	yes
Q86SQ7-2	2, e
Q86SQ7-3	3
Q86SQ7-4	4, b

RefSeq proteins (6): NP_001337175, NP_001337176, NP_001337177, NP_001337178, NP_001337180, NP_006633* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031887	SDCCAG8	Family

Pfam: PF15964

UniProt features (17 total): splice variant 5, region of interest 4, coiled-coil region 3, modified residue 2, chain 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SQ7-F1	78.67	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 28, 4

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-1640170	Cell Cycle
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 393 (showing top): GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, TGCGCANK_UNKNOWN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGAMTNNNNNTCCY_UNKNOWN, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, GOBP_ORGANELLE_ASSEMBLY, GOBP_NEURON_MIGRATION, GOBP_TUBE_FORMATION, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (7): neuron migration (GO:0001764), centrosome cycle (GO:0007098), establishment of cell polarity (GO:0030010), cell projection organization (GO:0030030), microtubule organizing center organization (GO:0031023), tube formation (GO:0035148), regulation of cilium assembly (GO:1902017)

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

GO Cellular Component (13): nucleoplasm (GO:0005654), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), cell-cell junction (GO:0005911), cilium (GO:0005929), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), photoreceptor cell cilium (GO:0097733), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Cell Cycle, Mitotic	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	1
M Phase	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
microtubule organizing center	3
cellular component organization	2
intracellular membraneless organelle	2
cell migration	1
generation of neurons	1
cell cycle process	1
microtubule organizing center organization	1
establishment or maintenance of cell polarity	1
microtubule cytoskeleton organization	1
microtubule-based process	1
tube morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cilium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of organelle assembly	1
binding	1
nuclear lumen	1
centriole	1
cytoplasm	1
anchoring junction	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
centrosome	1
cilium	1
neuron projection	1
9+0 non-motile cilium	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1758 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDCCAG8	IQCB1	Q15051	963
SDCCAG8	OFD1	O75665	959
SDCCAG8	NPHP3	Q7Z494	884
SDCCAG8	NPHP4	O75161	872
SDCCAG8	NIN	Q8N4C6	864
SDCCAG8	CEP290	O15078	858
SDCCAG8	NPHP1	O15259	850
SDCCAG8	RPGRIP1L	Q68CZ1	722
SDCCAG8	BBS1	Q8NFJ9	675
SDCCAG8	BBS10	Q8TAM1	674
SDCCAG8	MKS1	Q9NXB0	674
SDCCAG8	BBS12	Q6ZW61	667
SDCCAG8	TTC8	Q8TAM2	667
SDCCAG8	BBS4	Q96RK4	665
SDCCAG8	WDPCP	O95876	662

IntAct

46 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
SDCCAG8	OFD1	psi-mi:“MI:0914”(association)	0.710
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
SDCCAG8	RABEP2	psi-mi:“MI:0915”(physical association)	0.620
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
SDCCAG8	CEP131	psi-mi:“MI:0915”(physical association)	0.500
gag	SDCCAG8	psi-mi:“MI:0915”(physical association)	0.500
RUVBL1	SDCCAG8	psi-mi:“MI:0915”(physical association)	0.400
TSC1	SDCCAG8	psi-mi:“MI:0915”(physical association)	0.370
	SDCCAG8	psi-mi:“MI:0915”(physical association)	0.370
SDCCAG8		psi-mi:“MI:0915”(physical association)	0.370
Rab7a		psi-mi:“MI:0914”(association)	0.350
Ube2k	ZFTRAF1	psi-mi:“MI:0914”(association)	0.350
ORF21	USP9Y	psi-mi:“MI:0914”(association)	0.350
SDCCAG8	MYO1C	psi-mi:“MI:0914”(association)	0.350
SDCCAG8	ERC1	psi-mi:“MI:0914”(association)	0.350
KARS1	TARSL2	psi-mi:“MI:0914”(association)	0.350
LARS1	TARSL2	psi-mi:“MI:0914”(association)	0.350
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.350
SCARA3	DEGS1	psi-mi:“MI:0914”(association)	0.350
FXR1	TPD52L2	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
KARS1	TARS3	psi-mi:“MI:0914”(association)	0.350
LARS1	TARS3	psi-mi:“MI:0914”(association)	0.350
IARS1	TARS3	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): SDCCAG8 (Affinity Capture-MS), SDCCAG8 (Synthetic Lethality), SDCCAG8 (Two-hybrid), SDCCAG8 (Proximity Label-MS), SDCCAG8 (Affinity Capture-MS), SDCCAG8 (Affinity Capture-MS), SDCCAG8 (Affinity Capture-MS), SDCCAG8 (Affinity Capture-MS), SDCCAG8 (Affinity Capture-MS), SDCCAG8 (Affinity Capture-MS), SDCCAG8 (Affinity Capture-MS), OFD1 (Affinity Capture-MS), UBE2N (Affinity Capture-MS), SDCCAG8 (Affinity Capture-MS), SDCCAG8 (Affinity Capture-RNA)

ESM2 similar proteins: A0A2R8QCI3, A0JMK8, A3KGV1, A7YH32, A9X1A5, B0KWC9, B6MFW3, B8JK76, G5E861, G9G127, O35550, O35551, P59242, P85120, Q15276, Q3V6T2, Q502I3, Q5BJF6, Q5RG45, Q5SNZ0, Q5TZ80, Q5ZJ27, Q5ZKK5, Q66GS9, Q66KE8, Q6AYX5, Q6DIX6, Q6NRB0, Q6P402, Q6P5D4, Q6PGZ0, Q6VGS5, Q6ZU80, Q7TMK6, Q80UF4, Q80YF0, Q80YT7, Q86SQ7, Q8BIL5, Q8CJ99

Diamond homologs: B8JK76, Q80UF4, Q86SQ7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Loss of Nlp from mitotic centrosomes	5	31.7×	2e-05
Loss of proteins required for interphase microtubule organization from the centrosome	5	31.7×	2e-05
FCERI mediated NF-kB activation	5	31.3×	2e-05
AURKA Activation by TPX2	5	30.4×	2e-05
CLEC7A (Dectin-1) signaling	5	28.6×	2e-05
Recruitment of mitotic centrosome proteins and complexes	5	27.2×	3e-05
Downstream TCR signaling	5	25.7×	3e-05
Regulation of PLK1 Activity at G2/M Transition	5	25.4×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
obsolete positive regulation of NF-kappaB transcription factor activity	5	26.4×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	44
Likely pathogenic	44
Uncertain significance	369
Likely benign	219
Benign	23

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070303	NM_006642.5(SDCCAG8):c.784G>T (p.Glu262Ter)	Pathogenic
1400329	NM_006642.5(SDCCAG8):c.250C>T (p.Gln84Ter)	Pathogenic
1452529	NM_006642.5(SDCCAG8):c.234dup (p.Asp79fs)	Pathogenic
1456221	NC_000001.10:g.(?243303219)(243456541_?)del	Pathogenic
156528	NM_006642.5(SDCCAG8):c.1628_1631del (p.Asp543fs)	Pathogenic
156529	NM_006642.5(SDCCAG8):c.1444del (p.Thr482fs)	Pathogenic
1918532	NM_006642.5(SDCCAG8):c.46C>T (p.Gln16Ter)	Pathogenic
1955937	NM_006642.5(SDCCAG8):c.252del (p.Ala85fs)	Pathogenic
2006501	NM_006642.5(SDCCAG8):c.629dup (p.Asn210fs)	Pathogenic
2009850	NM_006642.5(SDCCAG8):c.849T>A (p.Cys283Ter)	Pathogenic
2048826	NM_006642.5(SDCCAG8):c.397G>T (p.Glu133Ter)	Pathogenic
2055381	NM_006642.5(SDCCAG8):c.553_554del (p.Met185fs)	Pathogenic
212139	NM_006642.5(SDCCAG8):c.221-2A>G	Pathogenic
212140	NM_006642.5(SDCCAG8):c.481C>T (p.Gln161Ter)	Pathogenic
2160069	NM_006642.5(SDCCAG8):c.82del (p.Ser28fs)	Pathogenic
2203016	NM_006642.5(SDCCAG8):c.1068+1G>A	Pathogenic
2633268	NM_006642.5(SDCCAG8):c.862C>T (p.Gln288Ter)	Pathogenic
287667	NM_006642.5(SDCCAG8):c.1159del (p.Ala387fs)	Pathogenic
2939244	NM_006642.5(SDCCAG8):c.1177del (p.Met392_Met393insTer)	Pathogenic
2942587	NM_006642.5(SDCCAG8):c.1418dup (p.Glu474fs)	Pathogenic
2951815	NM_006642.5(SDCCAG8):c.787C>T (p.Gln263Ter)	Pathogenic
3247836	NC_000001.10:g.(?243419466)(243663097_?)del	Pathogenic
3247837	NC_000001.10:g.(?243385006)(243480215_?)del	Pathogenic
3247839	NC_000001.10:g.(?243433387)(243437978_?)del	Pathogenic
3381773	NM_006642.5(SDCCAG8):c.1817_1818dup (p.Ala607Ter)	Pathogenic
3582590	NM_006642.5(SDCCAG8):c.849_852del (p.Leu282_Cys283insTer)	Pathogenic
3753397	NM_006642.5(SDCCAG8):c.1068+1G>T	Pathogenic
4689305	NM_006642.5(SDCCAG8):c.10del (p.Ser4fs)	Pathogenic
4786194	NM_006642.5(SDCCAG8):c.170dup (p.Asn58fs)	Pathogenic
4786384	NM_006642.5(SDCCAG8):c.52C>T (p.Gln18Ter)	Pathogenic

SpliceAI

5576 predictions. Top by Δscore:

Variant	Effect	Δscore
1:243256238:GGG:G	donor_gain	1.0000
1:243256239:GG:G	donor_gain	1.0000
1:243256239:GGG:G	donor_gain	1.0000
1:243256240:GG:G	donor_gain	1.0000
1:243256240:GGT:G	donor_loss	1.0000
1:243256241:GTG:G	donor_loss	1.0000
1:243256242:T:G	donor_loss	1.0000
1:243270253:TGCTG:T	donor_gain	1.0000
1:243270254:GCTG:G	donor_gain	1.0000
1:243270254:GCTGG:G	donor_gain	1.0000
1:243270258:G:GA	donor_loss	1.0000
1:243270258:G:GG	donor_gain	1.0000
1:243270259:T:G	donor_loss	1.0000
1:243270975:T:G	acceptor_gain	1.0000
1:243270976:A:AG	acceptor_gain	1.0000
1:243270977:G:GA	acceptor_gain	1.0000
1:243270977:GT:G	acceptor_gain	1.0000
1:243270977:GTT:G	acceptor_gain	1.0000
1:243270977:GTTA:G	acceptor_gain	1.0000
1:243270977:GTTAA:G	acceptor_gain	1.0000
1:243271059:CCTTG:C	donor_gain	1.0000
1:243271060:CTTG:C	donor_gain	1.0000
1:243271061:TTG:T	donor_gain	1.0000
1:243271061:TTGG:T	donor_loss	1.0000
1:243271062:TG:T	donor_gain	1.0000
1:243271062:TGGTA:T	donor_loss	1.0000
1:243271063:GG:G	donor_gain	1.0000
1:243271063:GGT:G	donor_loss	1.0000
1:243271064:G:GG	donor_gain	1.0000
1:243274541:A:AG	acceptor_gain	1.0000

AlphaMissense

4760 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:243489016:T:C	L663P	0.981
1:243415785:T:C	L567P	0.980
1:243316873:G:C	A350P	0.978
1:243489025:T:C	L666P	0.970
1:243489067:T:C	L680P	0.965
1:243344269:G:C	A471P	0.964
1:243274636:G:C	A134P	0.962
1:243330540:G:C	A357P	0.954
1:243489058:T:C	L677P	0.951
1:243418052:T:C	L610P	0.948
1:243426550:G:A	M659I	0.948
1:243426550:G:C	M659I	0.948
1:243426550:G:T	M659I	0.948
1:243308171:T:C	L308P	0.946
1:243378851:T:C	L535P	0.944
1:243330574:T:C	L368P	0.939
1:243489088:T:C	L687P	0.935
1:243344240:T:C	L461P	0.934
1:243316781:T:C	L319P	0.929
1:243308095:T:C	C283R	0.928
1:243415763:G:C	A560P	0.928
1:243489048:G:C	A674P	0.928
1:243489070:T:C	L681P	0.926
1:243286279:T:C	L143P	0.924
1:243418019:T:C	L599S	0.921
1:243341070:T:C	L418P	0.918
1:243426528:A:C	H652P	0.918
1:243426444:T:C	L624P	0.916
1:243308104:T:A	C286S	0.915
1:243308105:G:C	C286S	0.915

dbSNP variants (sampled 300 via entrez): RS1000025845 (1:243493328 TG>T,TGG), RS1000027849 (1:243331613 A>C), RS1000031925 (1:243343759 T>G), RS1000037311 (1:243446933 T>C), RS1000046171 (1:243435883 A>C), RS1000075515 (1:243281925 G>T), RS1000077879 (1:243466065 T>C), RS1000084532 (1:243422848 G>A,T), RS1000089735 (1:243319200 C>G,T), RS1000091837 (1:243376660 A>C), RS1000094538 (1:243444274 A>G,T), RS1000109533 (1:243459720 C>T), RS1000109969 (1:243395665 T>C), RS1000117626 (1:243495659 C>T), RS1000117962 (1:243479067 C>G,T)

Disease associations

OMIM: gene MIM:613524 | disease phenotypes: MIM:613615, MIM:615993, MIM:209900, MIM:266900

GenCC curated gene-disease

Disease	Classification	Inheritance
Senior-Loken syndrome 7	Definitive	Autosomal recessive
Bardet-Biedl syndrome 16	Strong	Autosomal recessive
ciliopathy	Strong	Autosomal recessive
Bardet-Biedl syndrome	Supportive	Autosomal recessive
Senior-Loken syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Bardet-Biedl syndrome 16	Definitive	AR

Mondo (8): Senior-Loken syndrome 7 (MONDO:0013326), Bardet-Biedl syndrome 16 (MONDO:0014444), Bardet-Biedl syndrome (MONDO:0015229), focal segmental glomerulosclerosis (MONDO:0100313), kidney disorder (MONDO:0005240), inherited retinal dystrophy (MONDO:0019118), Senior-Loken syndrome (MONDO:0017842), ciliopathy (MONDO:0005308)

Orphanet (3): Bardet-Biedl syndrome (Orphanet:110), Senior-Loken syndrome (Orphanet:3156), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

119 total (30 of 119 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000085	Horseshoe kidney
HP:0000090	Nephronophthisis
HP:0000100	Nephrotic syndrome
HP:0000104	Renal agenesis
HP:0000107	Renal cyst
HP:0000110	Renal dysplasia
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000147	Polycystic ovaries
HP:0000163	Abnormal oral cavity morphology
HP:0000218	High palate
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000426	Prominent nasal bridge
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures

GWAS associations

49 associations (top):

Study	Trait	p-value
GCST000663_3	Obesity (early onset extreme)	5.000000e-07
GCST002149_26	Schizophrenia	3.000000e-08
GCST002254_1	Schizophrenia, schizoaffective disorder or bipolar disorder	4.000000e-09
GCST002539_35	Schizophrenia	4.000000e-09
GCST002598_65	Educational attainment	2.000000e-06
GCST002671_2	Toenail selenium levels	6.000000e-06
GCST003372_27	Glomerular filtration rate (creatinine)	2.000000e-08
GCST004280_8	Diastolic blood pressure	7.000000e-16
GCST005141_74	Cognitive ability (MTAG)	4.000000e-09
GCST006166_48	Diastolic blood pressure x alcohol consumption interaction (2df test)	6.000000e-14
GCST006190_23	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-16
GCST006190_30	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-20
GCST006193_14	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-20
GCST006193_54	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-17
GCST006803_108	Schizophrenia	2.000000e-10
GCST006810_5	Self-reported risk-taking behaviour	7.000000e-11
GCST007094_192	Diastolic blood pressure	2.000000e-23
GCST007098_35	Diastolic blood pressure	5.000000e-13
GCST007098_36	Diastolic blood pressure	1.000000e-12
GCST007201_133	Schizophrenia	3.000000e-08
GCST007201_231	Schizophrenia	1.000000e-08
GCST007268_80	Diastolic blood pressure	5.000000e-15
GCST007269_62	Pulse pressure	3.000000e-09
GCST007325_59	General risk tolerance (MTAG)	5.000000e-21
GCST007344_23	Estimated glomerular filtration rate	1.000000e-08
GCST007876_145	Estimated glomerular filtration rate	2.000000e-11
GCST007920_8	Chronic kidney disease	2.000000e-16
GCST008058_81	Estimated glomerular filtration rate	9.000000e-23
GCST008059_81	Estimated glomerular filtration rate	1.000000e-20
GCST008064_41	Chronic kidney disease	4.000000e-17

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0006336	diastolic blood pressure
EFO:0004337	intelligence
EFO:0004329	alcohol drinking
EFO:0006527	smoking status measurement
EFO:0008579	risk-taking behaviour
EFO:0005763	pulse pressure measurement
EFO:0010130	health study participation
EFO:0010483	gentisic acid measurement
EFO:0007813	cotinine measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0010100	multisite chronic pain
EFO:0004980	appendicular lean mass
EFO:0007984	platelet component distribution width

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D058499	Retinal Dystrophies	C11.768.585.658
C537580	Senior Loken Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	8
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases methylation	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
vanadyl sulfate	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	decreases expression	1
Carbamazepine	affects expression	1
Carcinogens	decreases expression	1
Copper	affects binding, decreases expression	1
Estradiol	affects expression	1
Fluorouracil	increases expression	1
Methyl Methanesulfonate	increases expression	1
Mutagens	decreases expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1
Plant Extracts	affects cotreatment, increases expression	1
Selenium	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	PHASE4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	PHASE4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	PHASE4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease