ANKS6

Summary

ANKS6 (ankyrin repeat and sterile alpha motif domain containing 6, HGNC:26724) is a protein-coding gene on chromosome 9q22.33, encoding Ankyrin repeat and SAM domain-containing protein 6 (Q68DC2). Required for renal function. It is a selective cancer dependency (DepMap: 10.6% of cell lines).

This gene encodes a protein containing multiple ankyrin repeats and a SAM domain. It is thought that this protein may localize to the proximal region of the primary cilium, and may play a role in renal and cardiovascular development. Mutations in this gene have been shown to cause a form of nephronophthisis (NPHP16), a chronic tubulo-interstitial nephritis.

Source: NCBI Gene 203286 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephronophthisis 16 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 622 total — 20 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 17
• Cancer dependency (DepMap): dependent in 10.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_173551

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26724
Approved symbol	ANKS6
Name	ankyrin repeat and sterile alpha motif domain containing 6
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36928, NPHP16
Ensembl gene	ENSG00000165138
Ensembl biotype	protein_coding
OMIM	615370
Entrez	203286

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000353234, ENST00000375019, ENST00000444472, ENST00000466120, ENST00000471846, ENST00000486778, ENST00000634393, ENST00000927508, ENST00000941017

RefSeq mRNA: 1 — MANE Select: NM_173551 NM_173551

CCDS: CCDS43856

Canonical transcript exons

ENST00000353234 — 15 exons

Exon	Start	End
ENSE00001090636	98745559	98745675
ENSE00001090640	98751029	98751096
ENSE00001251907	98768081	98768250
ENSE00001251914	98770896	98771046
ENSE00001251932	98773877	98774080
ENSE00001465486	98790104	98790606
ENSE00001465494	98777405	98777454
ENSE00001465495	98778226	98778424
ENSE00001465496	98780189	98780337
ENSE00001465498	98782467	98782573
ENSE00001465499	98783953	98784157
ENSE00001536196	98756420	98756603
ENSE00001946117	98732009	98736623
ENSE00003473196	98784832	98784876
ENSE00003529726	98796133	98796555

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 94.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4777 / max 56.7938, expressed in 1531 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101700	4.2227	1497
101699	0.2550	121

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	94.79	gold quality
cerebellar cortex	UBERON:0002129	94.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.59	gold quality
pancreatic ductal cell	CL:0002079	94.32	silver quality
cerebellum	UBERON:0002037	93.58	gold quality
epithelial cell of pancreas	CL:0000083	87.88	silver quality
lower esophagus mucosa	UBERON:0035834	87.88	gold quality
right lobe of thyroid gland	UBERON:0001119	86.07	gold quality
left lobe of thyroid gland	UBERON:0001120	85.86	gold quality
ileal mucosa	UBERON:0000331	85.56	gold quality
body of stomach	UBERON:0001161	85.48	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.39	gold quality
thyroid gland	UBERON:0002046	85.38	gold quality
right frontal lobe	UBERON:0002810	85.07	gold quality
tibialis anterior	UBERON:0001385	84.97	silver quality
metanephros cortex	UBERON:0010533	84.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.18	gold quality
cerebellar vermis	UBERON:0004720	84.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.93	gold quality
stomach	UBERON:0000945	83.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.45	gold quality
substantia nigra	UBERON:0002038	83.39	gold quality
body of pancreas	UBERON:0001150	83.30	gold quality
spinal cord	UBERON:0002240	83.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.00	gold quality
lower esophagus	UBERON:0013473	82.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.93	gold quality
stromal cell of endometrium	CL:0002255	82.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.80	gold quality
endocervix	UBERON:0000458	82.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

118 targeting ANKS6, 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-3120-5P	100.00	65.56	965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-670-5P	99.67	69.94	1565

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 10.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• Location, sequence and structure of the gene encoding human SamCystin have been determined. (PMID:18434273)
• ANKS6 as a new NPHP family member that assembles a distinct module of nephronophthisis-associated proteins, encompassing NEK8, INVS and NPHP3. (PMID:23793029)
• Data indicate the importance of ANKS6 in human kidney development and suggest a mechanism by which mutations in ANKS6 may contribute to an nephronophthisis-like phenotype in chronic kidney disease. (PMID:24610927)
• Study finds that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer; study presents crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. (PMID:24998259)
• Biallelic ANKS6 mutations cause late-onset ciliopathy with chronic kidney disease through YAP dysregulation. (PMID:34740236)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Anks6	ENSMUSG00000066191
rattus_norvegicus	Anks6	ENSRNOG00000023309

Paralogs (2): HDLBP (ENSG00000115677), BICC1 (ENSG00000122870)

Protein

Protein identifiers

Ankyrin repeat and SAM domain-containing protein 6 — Q68DC2 (reviewed: Q68DC2)

Alternative names: Ankyrin repeat domain-containing protein 14, SamCystin, Sterile alpha motif domain-containing protein 6

All UniProt accessions (3): A0A0A0MRS7, Q68DC2, H7C163

UniProt curated annotations — full annotation on UniProt →

Function. Required for renal function.

Subunit / interactions. Homooligomer. Interacts with NEK8. Central component of a complex containing at least ANKS6, INVS, NEK8 and NPHP3. ANKS6 may organize complex assembly by linking INVS and NPHP3 to NEK8 and INVS may target the complex to the proximal ciliary axoneme. Interacts (via SAM domain) with BICC1 (via KH domains) in an RNA-dependent manner. Interacts (via SAM domain) with ANKS3 (via SAM domain).

Subcellular location. Cell projection. Cilium. Cytoplasm.

Post-translational modifications. Hydroxylated at Asn-138, most probably by HIF1AN. This hydroxylation results in decreased NEK8-binding.

Disease relevance. Nephronophthisis 16 (NPHP16) [MIM:615382] A form of nephronophthisis, a chronic tubulo-interstitial nephritis that progresses to end-stage renal failure. Some patients have cystic kidneys of normal size and no extrarenal manifestations, whereas others have enlarged renal size and severe extrarenal defects, including hypertrophic obstructive cardiomyopathy, aortic stenosis, pulmonary stenosis, patent ductus arteriosus, situs inversus, and periportal liver fibrosis. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The ankyrin repeats are necessary and sufficient for NEK8-binding. The SAM domain mediates interaction with the SAM domain of ANKS3.

Isoforms (3)

UniProt ID	Names	Canonical?
Q68DC2-1	1	yes
Q68DC2-3	2
Q68DC2-4	3

RefSeq proteins (1): NP_775822* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR051631	Ankyrin-KH/SAM_domain	Family

Pfam: PF00023, PF00536, PF12796

UniProt features (52 total): repeat 11, sequence variant 7, compositionally biased region 6, helix 6, region of interest 5, modified residue 4, sequence conflict 4, splice variant 3, mutagenesis site 3, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4NL9	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68DC2-F1	60.60	0.25

Functional residue map

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

Catalytic / active sites (1): 823 (essential for anks3 interaction)

Post-translational modifications (4): 138, 657, 734, 742

Mutagenesis-validated functional residues (3):

Position	Phenotype
798	loss of interaction with anks3.
811	loss of interaction with anks3.
823	loss of interaction with anks3.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (4): in utero embryonic development (GO:0001701), kidney development (GO:0001822), determination of left/right symmetry (GO:0007368), heart development (GO:0007507)

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

GO Cellular Component (4): cytoplasm (GO:0005737), ciliary inversin compartment (GO:0097543), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
animal organ development	2
chordate embryonic development	1
renal system development	1
determination of bilateral symmetry	1
left/right pattern formation	1
circulatory system development	1
binding	1
intracellular anatomical structure	1
cilium	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKS6	NEK8	Q86SG6	984
ANKS6	NEK9	Q8TD19	980
ANKS6	NPHP3	Q7Z494	973
ANKS6	INVS	Q9Y283	860
ANKS6	ANKS3	Q6ZW76	793
ANKS6	PENK	P01210	769
ANKS6	PRKD1	Q15139	763
ANKS6	NPHP1	O15259	688
ANKS6	BICC1	Q9H694	648
ANKS6	NPHP4	O75161	600
ANKS6	NEK7	Q8TDX7	570
ANKS6	IQCB1	Q15051	544
ANKS6	NEK6	Q9HC98	523
ANKS6	ATP5F1C	P36542	496
ANKS6	CHCHD3	Q9NX63	495

IntAct

89 interactions, top by confidence:

A	B	Type	Score
NEK7	ANKS6	psi-mi:“MI:0914”(association)	0.730
NEK8	ANKS6	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TMEM60	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
RTP2	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
BCL2L2	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
MARCHF5	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
C5	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
BET1	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
EMD	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
EMP1	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
PITPNC1	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
STX7	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
SMIM1	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
ANKS6	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (65): ANKS6 (Reconstituted Complex), ANKS6 (Proximity Label-MS), ANKS6 (Affinity Capture-MS), ANKS6 (Affinity Capture-MS), ANKS6 (Affinity Capture-MS), ANKS6 (Affinity Capture-MS), NEK7 (Affinity Capture-MS), DDX1 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), TIMM10 (Affinity Capture-MS), TIMM9 (Affinity Capture-MS), ANKS6 (Affinity Capture-MS), NEK8 (Affinity Capture-MS), ANKS6 (Affinity Capture-MS), ANKS6 (Affinity Capture-RNA)

ESM2 similar proteins: A0M8S4, A0M8T5, A1X157, B9EJA2, P0C0T2, P39880, P53564, P53565, Q00PJ1, Q07DV1, Q07DW4, Q07DX4, Q07DY4, Q07DZ5, Q07E15, Q07E28, Q07E41, Q09YG9, Q09YI1, Q09YJ3, Q09YK4, Q09YM8, Q108T9, Q13625, Q2IBA2, Q2IBB2, Q2IBD4, Q2IBE6, Q2IBF7, Q2IBF8, Q2QL82, Q2QLA2, Q2QLB3, Q2QLF8, Q2QLG9, Q53HC0, Q5RDH2, Q68DC2, Q6GQX6, Q6IPM2

Diamond homologs: A0A0R4IQZ2, A2AS55, A4II29, B4E2M5, C7B178, G0LXV8, L7X8P2, L7XCU0, L7XDS4, P0C0T2, P0C550, P0DJE3, P19838, P23631, P39010, Q04749, Q04861, Q0JKV1, Q10728, Q18297, Q28C34, Q337A0, Q38998, Q3SX00, Q3UMT1, Q3UX43, Q499M5, Q4JHE0, Q5H9F3, Q5R8C8, Q5U5A6, Q63369, Q68DC2, Q6FJ70, Q6GQX6, Q6NRD0, Q6NY19, Q6P6B7, Q6P9J5, Q6ZVH7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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
EML4 and NUDC in mitotic spindle formation	5	12.6×	2e-03
Mitotic Prometaphase	6	11.2×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein transport	7	6.3×	3e-03
cell division	6	5.7×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	12
Uncertain significance	320
Likely benign	175
Benign	35

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1031266	NM_173551.5(ANKS6):c.907+2T>A	Pathogenic
1695916	NM_173551.5(ANKS6):c.1672_1675dup (p.Pro559fs)	Pathogenic
1710087	NM_173551.5(ANKS6):c.1373G>A (p.Trp458Ter)	Pathogenic
2029697	NM_173551.5(ANKS6):c.1300del (p.Leu434fs)	Pathogenic
2183268	NM_173551.5(ANKS6):c.639G>A (p.Trp213Ter)	Pathogenic
2681749	NM_173551.5(ANKS6):c.651dup (p.Asn218fs)	Pathogenic
2881274	NM_173551.5(ANKS6):c.189_190del (p.Ala64fs)	Pathogenic
2883386	NM_173551.5(ANKS6):c.1683_1698dup (p.Phe567fs)	Pathogenic
2982283	NM_173551.5(ANKS6):c.1096C>T (p.Gln366Ter)	Pathogenic
3661824	NM_173551.5(ANKS6):c.1510dup (p.Gln504fs)	Pathogenic
3686362	NM_173551.5(ANKS6):c.154del (p.Ala52fs)	Pathogenic
4740223	NM_173551.5(ANKS6):c.433del (p.Ala145fs)	Pathogenic
503782	NM_173551.5(ANKS6):c.1301del (p.Leu434fs)	Pathogenic
571622	NM_173551.5(ANKS6):c.727C>T (p.Gln243Ter)	Pathogenic
574976	NM_173551.5(ANKS6):c.694_718dup (p.Val240fs)	Pathogenic
591737	NM_173551.5(ANKS6):c.130_157del (p.Glu44fs)	Pathogenic
64357	NM_173551.5(ANKS6):c.2054_2064del (p.His685fs)	Pathogenic
64358	NM_173551.5(ANKS6):c.2370_2372del (p.Tyr790_Gln791delinsTer)	Pathogenic
64359	NM_173551.5(ANKS6):c.2512-2A>C	Pathogenic
661012	NM_173551.5(ANKS6):c.539_540del (p.Leu180fs)	Pathogenic
1175179	NM_173551.5(ANKS6):c.2420dup (p.Thr808fs)	Likely pathogenic
1175180	NM_173551.5(ANKS6):c.1973-1G>A	Likely pathogenic
1710088	NM_173551.5(ANKS6):c.2394+1G>A	Likely pathogenic
2501784	NM_173551.5(ANKS6):c.2142G>T (p.Lys714Asn)	Likely pathogenic
3596035	NM_173551.5(ANKS6):c.2041C>T (p.Gln681Ter)	Likely pathogenic
3596039	NM_173551.5(ANKS6):c.1965_1966delinsA (p.Asn655fs)	Likely pathogenic
3596071	NM_173551.5(ANKS6):c.1318C>T (p.Arg440Ter)	Likely pathogenic
3596086	NM_173551.5(ANKS6):c.877C>T (p.Arg293Ter)	Likely pathogenic
3596109	NM_173551.5(ANKS6):c.478dup (p.Val160fs)	Likely pathogenic
3596114	NM_173551.5(ANKS6):c.363dup (p.Gly122fs)	Likely pathogenic

SpliceAI

2971 predictions. Top by Δscore:

Variant	Effect	Δscore
9:98751023:TCTTA:T	donor_loss	1.0000
9:98751024:CTTAC:C	donor_loss	1.0000
9:98751025:TTA:T	donor_loss	1.0000
9:98751026:TA:T	donor_loss	1.0000
9:98751027:A:AT	donor_loss	1.0000
9:98751100:CAAGA:C	acceptor_gain	1.0000
9:98751104:A:AC	acceptor_gain	1.0000
9:98751112:G:GC	acceptor_gain	1.0000
9:98773875:A:AC	donor_gain	1.0000
9:98773876:C:CC	donor_gain	1.0000
9:98773876:CA:C	donor_gain	1.0000
9:98778420:CAGGA:C	acceptor_gain	1.0000
9:98778421:AGGA:A	acceptor_gain	1.0000
9:98778422:GGA:G	acceptor_gain	1.0000
9:98778423:GA:G	acceptor_gain	1.0000
9:98778425:C:CC	acceptor_gain	1.0000
9:98778429:C:CT	acceptor_gain	1.0000
9:98778430:A:T	acceptor_gain	1.0000
9:98780338:C:CC	acceptor_gain	1.0000
9:98782465:A:AC	donor_gain	1.0000
9:98782466:C:A	donor_loss	1.0000
9:98782466:C:CC	donor_gain	1.0000
9:98782484:A:AC	donor_gain	1.0000
9:98782571:TTC:T	acceptor_gain	1.0000
9:98782572:TCC:T	acceptor_loss	1.0000
9:98782573:CCTGG:C	acceptor_loss	1.0000
9:98782574:C:CC	acceptor_gain	1.0000
9:98782574:CT:C	acceptor_loss	1.0000
9:98782575:T:C	acceptor_loss	1.0000
9:98783998:T:A	donor_gain	1.0000

AlphaMissense

5637 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:98745650:A:G	L807P	1.000
9:98745572:A:G	L833P	0.999
9:98745581:A:T	I830N	0.999
9:98745626:A:G	L815P	0.999
9:98745635:A:G	L812S	0.999
9:98745656:A:G	L805P	0.999
9:98745658:G:C	F804L	0.999
9:98745658:G:T	F804L	0.999
9:98745659:A:C	F804C	0.999
9:98745659:A:G	F804S	0.999
9:98745660:A:G	F804L	0.999
9:98751042:A:C	F794C	0.999
9:98751042:A:G	F794S	0.999
9:98751078:A:G	L782P	0.999
9:98782490:A:G	L399P	0.999
9:98782550:A:G	L379P	0.999
9:98783984:A:G	W361R	0.999
9:98783984:A:T	W361R	0.999
9:98736604:A:G	L844S	0.998
9:98745585:C:G	A829P	0.998
9:98745590:A:G	L827P	0.998
9:98745593:A:C	I826S	0.998
9:98745593:A:G	I826T	0.998
9:98751041:A:C	F794L	0.998
9:98751041:A:T	F794L	0.998
9:98751043:A:G	F794L	0.998
9:98751069:A:G	L785S	0.998
9:98751078:A:T	L782H	0.998
9:98782499:G:T	A396D	0.998
9:98783966:C:G	A367P	0.998

dbSNP variants (sampled 300 via entrez): RS1000006844 (9:98792482 A>C), RS1000040767 (9:98767580 A>T), RS1000053540 (9:98760677 C>A), RS1000075542 (9:98746346 T>C), RS1000077520 (9:98753305 A>G), RS1000085808 (9:98774908 A>G), RS1000133901 (9:98778937 C>T), RS1000155671 (9:98775888 G>A,C), RS1000204025 (9:98732581 A>C,G), RS1000233155 (9:98735303 T>C), RS1000281207 (9:98746674 G>A), RS1000304143 (9:98746581 G>C), RS1000370344 (9:98740943 G>A), RS1000376411 (9:98775632 A>C), RS1000389947 (9:98752204 A>C,G)

Disease associations

OMIM: gene MIM:615370 | disease phenotypes: MIM:615382

GenCC curated gene-disease

Disease	Classification	Inheritance
nephronophthisis 16	Definitive	Autosomal recessive
nephronophthisis 2	Supportive	Autosomal recessive
nephronophthisis 1	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nephronophthisis 16	Definitive	AR

Mondo (3): nephronophthisis 16 (MONDO:0014158), nephronophthisis 2 (MONDO:0011190), nephronophthisis 1 (MONDO:0009728)

Orphanet (1): Nephronophthisis (Orphanet:655)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000090	Nephronophthisis
HP:0000105	Enlarged kidney
HP:0000113	Polycystic kidney dysplasia
HP:0001396	Cholestasis
HP:0001405	Periportal fibrosis
HP:0001639	Hypertrophic cardiomyopathy
HP:0001642	Pulmonic stenosis
HP:0001643	Patent ductus arteriosus
HP:0001650	Aortic valve stenosis
HP:0001696	Situs inversus totalis
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003774	Stage 5 chronic kidney disease
HP:0011463	Childhood onset

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004904_46	Body mass index	3.000000e-08
GCST012466_3	Autism spectrum disorder	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C566582	Nephronophthisis 2 (supp.)
C537699	Nephronophthisis, familial juvenile (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression, increases expression	3
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
bisphenol S	increases methylation	1
NSC 689534	affects binding, decreases expression	1
Acetaminophen	increases expression	1
Copper	affects binding, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06648044	Not specified	RECRUITING	Research of Therapeutic Targets in the Frame of Nephronophthisis and Renal Associated Ciliopathies