KANK2

Summary

KANK2 (KN motif and ankyrin repeat domains 2, HGNC:29300) is a protein-coding gene on chromosome 19p13.2, encoding KN motif and ankyrin repeat domain-containing protein 2 (Q63ZY3). Involved in transcription regulation by sequestering in the cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3.

This gene encodes a member of the KN motif and ankyrin repeat domains (KANK) family of proteins, which play a role in cytoskeletal formation by regulating actin polymerization. The encoded protein functions in the sequestration of steroid receptor coactivators and possibly other proteins. Mutations in this gene are associated with impaired kidney podocyte function and nephrotic syndrome, and keratoderma and woolly hair.

Source: NCBI Gene 25959 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome 16 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 28
• Clinical variants (ClinVar): 563 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 29
• MANE Select transcript: NM_001136191

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29300
Approved symbol	KANK2
Name	KN motif and ankyrin repeat domains 2
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1518, SIP
Ensembl gene	ENSG00000197256
Ensembl biotype	protein_coding
OMIM	614610
Entrez	25959

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 38 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000586659, ENST00000587317, ENST00000588724, ENST00000588787, ENST00000589359, ENST00000589427, ENST00000589894, ENST00000590095, ENST00000590400, ENST00000590685, ENST00000592215, ENST00000592675, ENST00000592903, ENST00000884138, ENST00000884139, ENST00000884140, ENST00000884141, ENST00000884142, ENST00000884143, ENST00000884144, ENST00000884145, ENST00000884146, ENST00000884147, ENST00000884148, ENST00000884149, ENST00000884150, ENST00000884151, ENST00000884152, ENST00000884153, ENST00000884154, ENST00000884155, ENST00000924545, ENST00000924546, ENST00000960852, ENST00000960853, ENST00000960854, ENST00000960855, ENST00000960856, ENST00000960857, ENST00000960858, ENST00000960859, ENST00000960860, ENST00000960861

RefSeq mRNA: 19 — MANE Select: NM_001136191 NM_001136191, NM_001329451, NM_001379548, NM_001379549, NM_001379550, NM_001379551, NM_001379552, NM_001379553, NM_001379554, NM_001379555, NM_001379556, NM_001379557, NM_001379558, NM_001379559, NM_001379560, NM_001379561, NM_001379562, NM_001379563, NM_015493

CCDS: CCDS12255, CCDS54219

Canonical transcript exons

ENST00000586659 — 13 exons

Exon	Start	End
ENSE00000713327	11172981	11173123
ENSE00000713329	11174473	11174692
ENSE00000713331	11175902	11175989
ENSE00000713334	11176578	11176817
ENSE00000713336	11178345	11178447
ENSE00000713339	11178553	11178720
ENSE00000713342	11192831	11194042
ENSE00001608341	11195622	11195820
ENSE00002924207	11164270	11166611
ENSE00002959564	11197485	11197545
ENSE00003514128	11170048	11170248
ENSE00003540117	11194475	11194590
ENSE00003617559	11169877	11169966

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.2217 / max 2076.3846, expressed in 1651 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179198	32.4425	1620
179201	1.1161	696
179199	0.2340	116
179200	0.2050	76
179194	0.1662	62
179197	0.0579	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	99.57	gold quality
mucosa of stomach	UBERON:0001199	99.40	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.36	gold quality
lower esophagus	UBERON:0013473	99.33	gold quality
urethra	UBERON:0000057	99.31	gold quality
right coronary artery	UBERON:0001625	99.30	gold quality
body of uterus	UBERON:0009853	99.30	gold quality
popliteal artery	UBERON:0002250	99.21	gold quality
tibial artery	UBERON:0007610	99.21	gold quality
endocervix	UBERON:0000458	99.18	gold quality
sural nerve	UBERON:0015488	99.17	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.16	gold quality
left uterine tube	UBERON:0001303	99.11	gold quality
descending thoracic aorta	UBERON:0002345	99.10	gold quality
aorta	UBERON:0000947	99.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.00	gold quality
myometrium	UBERON:0001296	98.98	gold quality
right ovary	UBERON:0002118	98.95	gold quality
coronary artery	UBERON:0001621	98.91	gold quality
left coronary artery	UBERON:0001626	98.89	gold quality
thoracic aorta	UBERON:0001515	98.84	gold quality
stromal cell of endometrium	CL:0002255	98.81	gold quality
ascending aorta	UBERON:0001496	98.80	gold quality
gall bladder	UBERON:0002110	98.73	gold quality
left ovary	UBERON:0002119	98.67	gold quality
synovial joint	UBERON:0002217	98.54	gold quality
tibial nerve	UBERON:0001323	98.51	gold quality
apex of heart	UBERON:0002098	98.47	gold quality
nipple	UBERON:0002030	98.42	gold quality
calcaneal tendon	UBERON:0003701	98.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	27.60
E-GEOD-135922	yes	26.91
E-ANND-3	yes	22.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting KANK2, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-3150A-3P	99.76	64.44	1640

Literature-anchored findings (GeneRIF, showing 7)

• SIP, a novel ankyrin repeat containing protein, sequesters steroid receptor coactivators in the cytoplasm. (PMID:17476305)
• Using whole-exome sequencing, authors identified a homozygous missense c.2009C>T mutation in KANK2 (PMID:24671081)
• identified recessive mutations in kidney ankyrin repeat-containing protein 1 (KANK1), KANK2, and KANK4 in individuals with nephrotic syndrome. (PMID:25961457)
• liprin beta-1 is associated with expression of kank 1 and 2 proteins in melanoma (PMID:26739330)
• KANK2 protein is required for targeting microtubules to focal adhesions. (PMID:31114072)
• Nephrotic-syndrome-associated mutation of KANK2 induces pathologic binding competition with physiological interactor KIF21A. (PMID:34274317)
• Talin2 and KANK2 functionally interact to regulate microtubule dynamics, paclitaxel sensitivity and cell migration in the MDA-MB-435S melanoma cell line. (PMID:37460977)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kank2	ENSDARG00000018393
mus_musculus	Kank2	ENSMUSG00000032194
rattus_norvegicus	Kank2	ENSRNOG00000010643
drosophila_melanogaster	Kank	FBGN0027596
caenorhabditis_elegans		WBGENE00006882

Paralogs (3): KANK1 (ENSG00000107104), KANK4 (ENSG00000132854), KANK3 (ENSG00000186994)

Protein

Protein identifiers

KN motif and ankyrin repeat domain-containing protein 2 — Q63ZY3 (reviewed: Q63ZY3)

Alternative names: Ankyrin repeat domain-containing protein 25, Matrix-remodeling-associated protein 3, SRC-1-interacting protein

All UniProt accessions (5): Q63ZY3, K7EIU4, K7EL48, K7ERU2, K7ES05

UniProt curated annotations — full annotation on UniProt →

Function. Involved in transcription regulation by sequestering in the cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3. Involved in regulation of caspase-independent apoptosis by sequestering the proapoptotic factor AIFM1 in mitochondria. Pro-apoptotic stimuli can induce its proteasomal degradation allowing the translocation of AIFM1 to the nucleus to induce apoptosis. Involved in the negative control of vitamin D receptor signaling pathway. Involved in actin stress fibers formation through its interaction with ARHGDIA and the regulation of the Rho signaling pathway. May thereby play a role in cell adhesion and migration, regulating for instance podocytes migration during development of the kidney. Through the Rho signaling pathway may also regulate cell proliferation.

Subunit / interactions. Interacts (non-phosphorylated form) with NCOA1; NCOA2 AND NCOA3. Interacts with AIFM1. Interacts with ARHGDIA; the interaction is direct and may regulate the interaction of ARHGDIA with RHOA, RAC1 and CDC42. Interacts (via ANK repeats 1-5) with KIF21A (via residues 1146-1167).

Subcellular location. Cytoplasm. Mitochondrion.

Tissue specificity. Strongly expressed in cervix, colon, heart, kidney and lung. Expressed in kidney glomerular podocytes and mesangial cells (at protein level).

Post-translational modifications. Phosphorylated by casein kinase II upon estrogen stimulation. Phosphorylation induces the release by KANK2 of NCOA1 and its translocation to the nucleus where NCOA1 can activate gene transcription.

Disease relevance. Palmoplantar keratoderma and woolly hair (PPKWH) [MIM:616099] A disorder characterized by abnormal thickening of the skin on the palms and soles, in association with woolly scalp hair. Affected individuals manifest a variable degree of striate palmoplantar keratoderma, generally more severe on the soles. Leukonychia is more pronounced on the fingernails than toenails. Scalp hair, body hair, eyebrows, and eyelashes are sparse. The fifth toes show variable degrees of pseudoainhum, ranging from external rotation to a deep sulcus at the digitoplantar fold, accompanied by a bulbous appearance of the distal toe. The disease is caused by variants affecting the gene represented in this entry. Nephrotic syndrome 16 (NPHS16) [MIM:617783] A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS16 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q63ZY3-1	1	yes
Q63ZY3-2	2
Q63ZY3-3	3

RefSeq proteins (19): NP_001129663, NP_001316380, NP_001366477, NP_001366478, NP_001366479, NP_001366480, NP_001366481, NP_001366482, NP_001366483, NP_001366484, NP_001366485, NP_001366486, NP_001366487, NP_001366488, NP_001366489, NP_001366490, NP_001366491, NP_001366492, NP_056308 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR021939	KN_motif	Conserved_site
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR047184	KANK1-4	Family

Pfam: PF00023, PF12075, PF12796

UniProt features (70 total): helix 17, modified residue 14, compositionally biased region 7, repeat 6, region of interest 6, mutagenesis site 6, sequence variant 5, splice variant 3, coiled-coil region 2, chain 1, sequence conflict 1, strand 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6TMD	X-RAY DIFFRACTION	1.5
4HBD	X-RAY DIFFRACTION	1.72
5YBV	X-RAY DIFFRACTION	2.12

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q63ZY3-F1	60.58	0.27

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 (14): 19, 83, 86, 89, 92, 105, 168, 323, 329, 356, 375, 472, 540, 552

Mutagenesis-validated functional residues (6):

Position	Phenotype
510–512	impairs phosphorylation; when associated with a-515.
515	impairs phosphorylation; when associated with 510-a–a-512.
702	4-fold decrease in binding to kif21a.
702	33-fold decrease in binding to kif21a.
803	26-fold decrease in binding to kif21a.
805	20-fold decrease in binding to kif21a.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 358 (showing top): MORF_RAGE, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, MORF_ATRX, GCM_ZNF198, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_ESTROGEN_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), apoptotic process (GO:0006915), negative regulation of cell population proliferation (GO:0008285), negative regulation of actin filament polymerization (GO:0030837), negative regulation of intracellular estrogen receptor signaling pathway (GO:0033147), regulation of Rho protein signal transduction (GO:0035023), negative regulation of programmed cell death (GO:0043069), negative regulation of vitamin D receptor signaling pathway (GO:0070563), kidney epithelium development (GO:0072073), podocyte cell migration (GO:0090521), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134)

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

GO Cellular Component (2): cytoplasm (GO:0005737), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	2
negative regulation of cellular process	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
actin filament polymerization	1
regulation of actin filament polymerization	1
negative regulation of protein polymerization	1
negative regulation of cytoskeleton organization	1
negative regulation of supramolecular fiber organization	1
estrogen receptor signaling pathway	1
negative regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of intracellular estrogen receptor signaling pathway	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
regulation of programmed cell death	1
vitamin D receptor signaling pathway	1
regulation of vitamin D receptor signaling pathway	1
negative regulation of intracellular signal transduction	1
kidney development	1
epithelium development	1
epithelial cell migration	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KANK2	ARHGDIA	P52565	849
KANK2	PPFIBP1	Q86W92	653
KANK2	TLN2	Q9Y4G6	648
KANK2	TLN1	Q9Y490	626
KANK2	SPC24	Q8NBT2	615
KANK2	PSEN1	P49768	582
KANK2	PSEN2	P49810	582
KANK2	FERMT2	Q96AC1	576
KANK2	NPRL3	Q12980	540
KANK2	VCL	P18206	528
KANK2	SYNPO	Q8N3V7	528
KANK2	ARHGAP24	Q8N264	524
KANK2	PXN	P49023	518
KANK2	RHOA	P06749	514
KANK2	KANK4	Q5T7N3	503

IntAct

731 interactions, top by confidence:

A	B	Type	Score
DYNLL1	KANK2	psi-mi:“MI:0915”(physical association)	0.870
KANK2	EIF4E	psi-mi:“MI:0915”(physical association)	0.780
GOLGA2	KANK2	psi-mi:“MI:0915”(physical association)	0.780
KANK2	GOLGA2	psi-mi:“MI:0915”(physical association)	0.780
EIF4E	KANK2	psi-mi:“MI:0915”(physical association)	0.780
MAGEB4	KANK2	psi-mi:“MI:0915”(physical association)	0.720
KANK2	LMO1	psi-mi:“MI:0915”(physical association)	0.720
KANK2	LMO4	psi-mi:“MI:0915”(physical association)	0.720
KANK2	FHL2	psi-mi:“MI:0915”(physical association)	0.720
KANK2	TXLNA	psi-mi:“MI:0915”(physical association)	0.720
IHO1	KANK2	psi-mi:“MI:0915”(physical association)	0.720
CEP70	KANK2	psi-mi:“MI:0915”(physical association)	0.720
KANK2	ABI3	psi-mi:“MI:0915”(physical association)	0.720
KANK2	MOB1A	psi-mi:“MI:0915”(physical association)	0.720
KANK2	MAGEB4	psi-mi:“MI:0915”(physical association)	0.720
LMO1	KANK2	psi-mi:“MI:0915”(physical association)	0.720
LMO4	KANK2	psi-mi:“MI:0915”(physical association)	0.720
FHL2	KANK2	psi-mi:“MI:0915”(physical association)	0.720
TXLNA	KANK2	psi-mi:“MI:0915”(physical association)	0.720
KANK2	IHO1	psi-mi:“MI:0915”(physical association)	0.720
ABI3	KANK2	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (347): KANK2 (Two-hybrid), KANK2 (Two-hybrid), KANK2 (Two-hybrid), KANK2 (Two-hybrid), KANK2 (Two-hybrid), KANK2 (Two-hybrid), KANK2 (Two-hybrid), KANK2 (Two-hybrid), KANK2 (Two-hybrid), KANK2 (Two-hybrid), KANK2 (Two-hybrid), KANK2 (Two-hybrid), GPSM1 (Two-hybrid), ABI3 (Two-hybrid), MOB1A (Two-hybrid)

ESM2 similar proteins: A0A8I3QA39, A1YB07, A2A6T1, A2A9T0, A2AHG0, A5PKL7, A6NKD9, A7MCY6, B8A5S6, D3ZD05, E1BEQ5, E1U8D0, E9Q6B2, F1MRK3, G3V735, O14529, O60299, O75145, O94964, P60469, Q1LZH7, Q3LUD4, Q3UIL6, Q499E4, Q5JTD0, Q5RCR6, Q5XIA0, Q62036, Q63ZY3, Q6DG50, Q6IQ23, Q6NZT2, Q6PDH0, Q86UU1, Q86X02, Q8BX02, Q8C7U1, Q8IY63, Q8K1Q4, Q8K371

Diamond homologs: D3ZD05, E9Q238, Q14678, Q1LZH7, Q5T7N3, Q63ZY3, Q6NY19, Q6P9J5, Q8BX02, Q9Z1P7, X1WE18, P93002, Q68DC2, A4II29, F1MJR8, O08764, O83515, P0C0T2, Q05823, Q05921, Q21920, Q24009, Q3KP44, Q502M6, Q5M9H0, Q5SUE8, Q5U4T7, Q5U5A6, Q5XJ13, Q6AI12, Q6GQX6, Q6ZW76, Q7T3X9, Q7T3Y0, Q7Z6K4, Q8BLD6, Q91ZA8, Q94CT7, Q99MQ1, Q9CZK6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	298
Likely benign	172
Benign	48

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
158088	NM_001136191.3(KANK2):c.2009C>T (p.Ala670Val)	Pathogenic
446388	NM_001136191.3(KANK2):c.2027C>T (p.Ser676Phe)	Pathogenic
4759253	NM_001136191.3(KANK2):c.1491del (p.Ser498fs)	Likely pathogenic

SpliceAI

2173 predictions. Top by Δscore:

Variant	Effect	Δscore
19:11166612:C:CC	acceptor_gain	1.0000
19:11169869:AGACT:A	donor_loss	1.0000
19:11169870:GACTC:G	donor_loss	1.0000
19:11169871:ACTC:A	donor_loss	1.0000
19:11169872:CT:C	donor_loss	1.0000
19:11169874:CACCG:C	donor_loss	1.0000
19:11169875:A:AC	donor_gain	1.0000
19:11169876:C:CC	donor_gain	1.0000
19:11169876:C:CT	donor_loss	1.0000
19:11170046:A:AC	donor_gain	1.0000
19:11170047:C:CA	donor_gain	1.0000
19:11170047:CG:C	donor_gain	1.0000
19:11170047:CGCG:C	donor_gain	1.0000
19:11170047:CGCGA:C	donor_gain	1.0000
19:11170245:CTGC:C	acceptor_gain	1.0000
19:11170246:TGC:T	acceptor_gain	1.0000
19:11170247:GC:G	acceptor_gain	1.0000
19:11170248:CC:C	acceptor_gain	1.0000
19:11170249:C:CA	acceptor_loss	1.0000
19:11170249:C:CC	acceptor_gain	1.0000
19:11170250:T:A	acceptor_loss	1.0000
19:11172976:CATA:C	donor_loss	1.0000
19:11172977:ATAC:A	donor_loss	1.0000
19:11172978:TACC:T	donor_loss	1.0000
19:11172979:A:C	donor_loss	1.0000
19:11172980:C:CT	donor_loss	1.0000
19:11172980:CCTGG:C	donor_gain	1.0000
19:11174404:C:A	donor_gain	1.0000
19:11174472:CCG:C	donor_gain	1.0000
19:11174689:CTTT:C	acceptor_gain	1.0000

AlphaMissense

5448 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:11174662:A:G	W627R	1.000
19:11174662:A:T	W627R	1.000
19:11193475:A:G	L202P	1.000
19:11193943:A:G	F46S	1.000
19:11173098:G:C	N698K	0.999
19:11173098:G:T	N698K	0.999
19:11174484:A:G	L686P	0.999
19:11174660:C:A	W627C	0.999
19:11174660:C:G	W627C	0.999
19:11193445:A:G	L212P	0.999
19:11193484:A:G	L199P	0.999
19:11193493:A:G	L196P	0.999
19:11193505:A:C	M192R	0.999
19:11193922:A:T	I53N	0.999
19:11193940:A:G	L47P	0.999
19:11193942:G:C	F46L	0.999
19:11193942:G:T	F46L	0.999
19:11193943:A:C	F46C	0.999
19:11193944:A:G	F46L	0.999
19:11193955:A:G	L42P	0.999
19:11169941:G:T	A813D	0.998
19:11174532:G:T	A670D	0.998
19:11174537:G:C	N668K	0.998
19:11174537:G:T	N668K	0.998
19:11174607:A:G	L645P	0.998
19:11175969:A:G	L594P	0.998
19:11193403:A:G	L226P	0.998
19:11193505:A:T	M192K	0.998
19:11193934:T:C	Y49C	0.998
19:11193962:A:C	Y40D	0.998

dbSNP variants (sampled 300 via entrez): RS1000004574 (19:11174974 G>T), RS1000008457 (19:11182105 G>A), RS1000028013 (19:11168002 C>G,T), RS1000126154 (19:11187101 C>G), RS1000183220 (19:11173384 C>T), RS1000189667 (19:11164146 C>T), RS1000215774 (19:11190395 T>G), RS1000263884 (19:11187714 A>G,T), RS1000449067 (19:11192271 C>T), RS1000606403 (19:11186527 G>A), RS1000882124 (19:11192579 G>A), RS1000900891 (19:11181910 T>C), RS1000939218 (19:11195546 C>T), RS1001064054 (19:11165955 G>A), RS1001069444 (19:11172245 G>A)

Disease associations

OMIM: gene MIM:614610 | disease phenotypes: MIM:616099, MIM:617783

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome 16	Strong	Autosomal recessive
wooly hair-palmoplantar keratoderma syndrome	Supportive	Autosomal recessive

Mondo (2): wooly hair-palmoplantar keratoderma syndrome (MONDO:0014492), nephrotic syndrome 16 (MONDO:0033280)

Orphanet (1): Woolly hair-palmoplantar keratoderma syndrome (Orphanet:420686)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000653	Sparse eyelashes
HP:0000707	Abnormality of the nervous system
HP:0000737	Irritability
HP:0000790	Hematuria
HP:0000969	Edema
HP:0000982	Palmoplantar keratoderma
HP:0001820	Leukonychia
HP:0001945	Fever
HP:0001967	Diffuse mesangial sclerosis
HP:0002027	Abdominal pain
HP:0002209	Sparse scalp hair
HP:0002224	Woolly hair
HP:0002231	Sparse body hair
HP:0002315	Headache
HP:0002586	Peritonitis
HP:0003073	Hypoalbuminemia
HP:0003774	Stage 5 chronic kidney disease
HP:0009775	Amniotic constriction ring
HP:0011463	Childhood onset
HP:0011947	Respiratory tract infection
HP:0012579	Minimal change glomerulonephritis
HP:0012622	Chronic kidney disease
HP:0031504	Foamy urine
HP:0045075	Sparse eyebrow
HP:0100539	Periorbital edema

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST001904_5	HDL cholesterol	3.000000e-09
GCST003302_3	Cholesterol, total	8.000000e-09
GCST004611_149	High light scatter reticulocyte count	3.000000e-160
GCST004612_96	High light scatter reticulocyte percentage of red cells	4.000000e-159
GCST004619_3	Reticulocyte fraction of red cells	3.000000e-57
GCST004621_207	Red cell distribution width	1.000000e-09
GCST004622_73	Reticulocyte count	2.000000e-56
GCST004628_111	Immature fraction of reticulocytes	4.000000e-87
GCST004628_112	Immature fraction of reticulocytes	1.000000e-236
GCST005196_234	Coronary artery disease	2.000000e-08
GCST006804_135	Red cell distribution width	6.000000e-10
GCST009725_92	Intraocular pressure	4.000000e-06
GCST010204_42	Low density lipoprotein cholesterol levels	0.000000e+00
GCST010243_113	Apolipoprotein B levels	3.000000e-12
GCST010244_400	Triglyceride levels	3.000000e-10
GCST011683_7	Low density lipoprotein cholesterol levels	9.000000e-08
GCST011694_6	Non-HDL cholesterol levels	4.000000e-07
GCST90002385_495	High light scatter reticulocyte count	8.000000e-264
GCST90002385_496	High light scatter reticulocyte count	3.000000e-12
GCST90002386_65	High light scatter reticulocyte percentage of red cells	2.000000e-263
GCST90002386_66	High light scatter reticulocyte percentage of red cells	5.000000e-12
GCST90002387_42	Immature fraction of reticulocytes	2.000000e-141
GCST90002387_43	Immature fraction of reticulocytes	3.000000e-15
GCST90002387_44	Immature fraction of reticulocytes	1.000000e-20
GCST90002397_185	Mean spheric corpuscular volume	1.000000e-12
GCST90002404_561	Red cell distribution width	6.000000e-34
GCST90002405_534	Reticulocyte count	1.000000e-161
GCST90002406_486	Reticulocyte fraction of red cells	5.000000e-166

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0004695	intraocular pressure measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0005689	non-high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
bisphenol A	decreases expression, decreases methylation	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Valproic Acid	affects expression, decreases expression, increases methylation	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha phellandrene	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
celastrol	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
entinostat	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1

Clinical trials (associated diseases)

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