KANK3

Summary

KANK3 (KN motif and ankyrin repeat domains 3, HGNC:24796) is a protein-coding gene on chromosome 19p13.2, encoding KN motif and ankyrin repeat domain-containing protein 3 (Q6NY19). May be involved in the control of cytoskeleton formation by regulating actin polymerization.

Predicted to be involved in negative regulation of actin filament polymerization. Predicted to be active in cytoplasm and cytoskeleton.

Source: NCBI Gene 256949 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 168 total
• MANE Select transcript: NM_198471

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24796
Approved symbol	KANK3
Name	KN motif and ankyrin repeat domains 3
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ46061
Ensembl gene	ENSG00000186994
Ensembl biotype	protein_coding
OMIM	614611
Entrez	256949

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 25 protein_coding, 1 retained_intron

ENST00000330915, ENST00000593331, ENST00000593649, ENST00000595639, ENST00000868859, ENST00000868860, ENST00000868861, ENST00000868862, ENST00000868863, ENST00000868864, ENST00000868865, ENST00000868866, ENST00000868867, ENST00000868868, ENST00000868869, ENST00000868870, ENST00000930064, ENST00000930065, ENST00000948262, ENST00000948263, ENST00000948264, ENST00000948265, ENST00000948266, ENST00000948267, ENST00000948268, ENST00000948269

RefSeq mRNA: 1 — MANE Select: NM_198471 NM_198471

CCDS: CCDS12199

Canonical transcript exons

ENST00000330915 — 11 exons

Exon	Start	End
ENSE00001312100	8343225	8343262
ENSE00001325843	8337795	8337856
ENSE00001340919	8324449	8324547
ENSE00001340921	8324630	8324830
ENSE00001340923	8324951	8325096
ENSE00001340926	8333014	8333230
ENSE00001340928	8333724	8333808
ENSE00001340932	8333910	8334116
ENSE00001340934	8334320	8334419
ENSE00001340936	8322584	8322922
ENSE00001487388	8334500	8335792

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 96.28.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7108 / max 25.6634, expressed in 279 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178940	0.7108	279

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	96.28	gold quality
apex of heart	UBERON:0002098	94.84	gold quality
olfactory bulb	UBERON:0002264	94.80	gold quality
type B pancreatic cell	CL:0000169	94.37	gold quality
right lung	UBERON:0002167	94.02	gold quality
pericardium	UBERON:0002407	93.28	gold quality
diaphragm	UBERON:0001103	91.95	gold quality
body of tongue	UBERON:0011876	91.90	silver quality
tendon of biceps brachii	UBERON:0008188	91.20	gold quality
upper lobe of left lung	UBERON:0008952	90.71	gold quality
spleen	UBERON:0002106	90.53	gold quality
upper lobe of lung	UBERON:0008948	89.66	gold quality
tongue	UBERON:0001723	89.54	silver quality
pharyngeal mucosa	UBERON:0000355	89.49	silver quality
cardia of stomach	UBERON:0001162	89.38	silver quality
peritoneum	UBERON:0002358	89.21	gold quality
omental fat pad	UBERON:0010414	89.21	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.07	gold quality
trachea	UBERON:0003126	88.47	silver quality
subcutaneous adipose tissue	UBERON:0002190	88.42	gold quality
cardiac ventricle	UBERON:0002082	88.33	gold quality
heart left ventricle	UBERON:0002084	88.33	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.31	gold quality
saphenous vein	UBERON:0007318	88.19	silver quality
superior surface of tongue	UBERON:0007371	87.68	gold quality
adipose tissue	UBERON:0001013	87.67	gold quality
dorsal plus ventral thalamus	UBERON:0001897	87.64	silver quality
inferior vagus X ganglion	UBERON:0005363	87.24	silver quality
pons	UBERON:0000988	87.19	silver quality
subthalamic nucleus	UBERON:0001906	87.14	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	256.95
E-MTAB-6701	yes	10.93
E-ANND-3	yes	5.20
E-MTAB-8060	no	50.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting KANK3, 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-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-4286	97.20	64.37	1587

Literature-anchored findings (GeneRIF, showing 3)

• Authors identified KANK3 as a new substrate for the oxygen sensor hypoxia-inducible factor 1-alpha inhibitor (HIF1AN), which hydroxylates HIF-1/2alpha and other ankyrin repeat domain-containing proteins at asparagine residues. (PMID:29047187)
• KANK family proteins in cancer. (PMID:33309958)
• KANK3 mediates the p38 MAPK pathway to regulate the proliferation and invasion of lung adenocarcinoma cells. (PMID:36463587)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kank3	ENSMUSG00000042099
rattus_norvegicus	Kank3	ENSRNOG00000007230
drosophila_melanogaster	Kank	FBGN0027596
caenorhabditis_elegans		WBGENE00006882

Paralogs (3): KANK1 (ENSG00000107104), KANK4 (ENSG00000132854), KANK2 (ENSG00000197256)

Protein

Protein identifiers

KN motif and ankyrin repeat domain-containing protein 3 — Q6NY19 (reviewed: Q6NY19)

Alternative names: Ankyrin repeat domain-containing protein 47

All UniProt accessions (2): M0QZJ3, Q6NY19

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the control of cytoskeleton formation by regulating actin polymerization.

Tissue specificity. Strongly expressed in breast, liver, lung, skeletal muscle and kidney.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6NY19-2	2	yes
Q6NY19-1	1

RefSeq proteins (1): NP_940873* (*=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: PF12075, PF12796

UniProt features (34 total): modified residue 9, compositionally biased region 8, repeat 5, region of interest 5, sequence variant 3, coiled-coil region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NY19-F1	65.25	0.31

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 (9): 152, 160, 164, 167, 168, 177, 271, 280, 293

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (1): negative regulation of actin filament polymerization (GO:0030837)

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

GO Cellular Component (2): cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KANK3	PHLDA3	Q9Y5J5	537
KANK3	CCDC73	Q6ZRK6	525
KANK3	RPS28	P25112	432
KANK3	VCL	P18206	419
KANK3	CYFIP2	Q96F07	416
KANK3	PRRG3	Q9BZD7	405
KANK3	SULF2	Q8IWU5	394
KANK3	MTURN	Q8N3F0	359
KANK3	SSX3	Q99909	354
KANK3	TPR	P12270	344
KANK3	ANGPTL4	Q9BY76	338
KANK3	TMEM165	Q9HC07	334
KANK3	ZNF414	Q96IQ9	327
KANK3	INPP5D	Q92835	323
KANK3	CRIP2	P52943	314

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
PPP1CC	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
KANK3	hisD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): KANK3 (Affinity Capture-RNA), KANK3 (Affinity Capture-MS), KANK3 (Affinity Capture-MS), KANK3 (Affinity Capture-RNA), KANK3 (Proximity Label-MS), KANK3 (Proximity Label-MS), KANK3 (Proximity Label-MS), KANK3 (Proximity Label-MS), KANK3 (Proximity Label-MS), KANK3 (Proximity Label-MS), KANK3 (Proximity Label-MS), KANK3 (Proximity Label-MS), KANK3 (Proximity Label-MS), KANK3 (Proximity Label-MS), KANK3 (Proximity Label-MS)

ESM2 similar proteins: A0A0U1RQ45, A0A0U1RQS6, A0A286YF58, A0A2R8YCJ5, A0A7I2V3R4, A2A699, A2VDX9, A6NCS6, A6NGB7, A6NJG2, A6NKF7, A6NKL6, A6NLJ0, A8MVW0, B2RU40, B7Z1M9, B8ZZ34, C9JH25, C9JVW0, D4A9R4, J3QNX5, M0QZC1, P03971, P0CG09, P0DPE3, Q0PHV7, Q0VD38, Q14761, Q29RK8, Q29RM6, Q2KJ18, Q2M3G4, Q2M3V2, Q5T442, Q64697, Q69YZ2, Q6F5E0, Q6NY19, Q6UXK2, Q80XF7

Diamond homologs: A2AQH4, A2AS55, A4II29, A5WVX9, A6QR20, B4E2M5, D3Z7P3, E9PTT0, G5EGA3, O83515, O94925, P13264, Q01317, Q15653, Q21920, Q3SX45, Q3U0L2, Q499M5, Q4FE45, Q4JHE0, Q502K3, Q54HW1, Q5H9F3, Q5U5A6, Q6NSI1, Q6NY19, Q6P6B7, Q7T3Y0, Q7Z6K4, Q80TN5, Q8IUH5, Q91ZA8, Q9BQI6, Q9CQ31, Q9VUW9, Q9XZC0, Q9Z2F6, A0A0R4IQZ2, C7B178, G0LXV8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	148
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1906 predictions. Top by Δscore:

Variant	Effect	Δscore
19:8324444:CTCA:C	donor_loss	1.0000
19:8324445:TCA:T	donor_loss	1.0000
19:8324445:TCACC:T	donor_loss	1.0000
19:8324446:CA:C	donor_loss	1.0000
19:8324447:A:AT	donor_loss	1.0000
19:8324447:A:C	donor_loss	1.0000
19:8324448:C:CA	donor_loss	1.0000
19:8324448:C:CT	donor_loss	1.0000
19:8324543:CCCTC:C	acceptor_gain	1.0000
19:8324544:CCTCC:C	acceptor_gain	1.0000
19:8324545:CTC:C	acceptor_gain	1.0000
19:8324546:TC:T	acceptor_gain	1.0000
19:8324547:CC:C	acceptor_gain	1.0000
19:8324548:C:CC	acceptor_gain	1.0000
19:8324548:CTGT:C	acceptor_loss	1.0000
19:8324624:TCTTA:T	donor_loss	1.0000
19:8324625:CTTAC:C	donor_loss	1.0000
19:8324626:TTAC:T	donor_loss	1.0000
19:8324626:TTACA:T	donor_loss	1.0000
19:8324627:TACAT:T	donor_loss	1.0000
19:8324628:A:AC	donor_gain	1.0000
19:8324628:A:T	donor_loss	1.0000
19:8324629:C:CA	donor_loss	1.0000
19:8324629:C:CC	donor_gain	1.0000
19:8324629:CA:C	donor_gain	1.0000
19:8324826:CCCGT:C	acceptor_gain	1.0000
19:8324827:CCGTC:C	acceptor_gain	1.0000
19:8324828:CGT:C	acceptor_gain	1.0000
19:8324831:C:CC	acceptor_gain	1.0000
19:8324838:G:GC	acceptor_gain	1.0000

AlphaMissense

5223 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:8333203:A:G	W583R	0.997
19:8333203:A:T	W583R	0.997
19:8333060:A:C	S630R	0.996
19:8333060:A:T	S630R	0.996
19:8333062:T:G	S630R	0.996
19:8324702:A:C	S737R	0.995
19:8324702:A:T	S737R	0.995
19:8324704:T:G	S737R	0.995
19:8333078:G:C	N624K	0.995
19:8333078:G:T	N624K	0.995
19:8325071:G:C	N654K	0.994
19:8325071:G:T	N654K	0.994
19:8333201:C:A	W583C	0.994
19:8333201:C:G	W583C	0.994
19:8324522:G:T	A770D	0.992
19:8324670:A:G	L748P	0.992
19:8333073:G:T	A626D	0.992
19:8334340:A:C	F469L	0.991
19:8334340:A:T	F469L	0.991
19:8334342:A:G	F469L	0.991
19:8324670:A:T	L748Q	0.990
19:8324534:G:T	A766D	0.989
19:8324814:A:T	L700H	0.988
19:8333053:G:C	H633D	0.987
19:8324706:G:T	A736D	0.986
19:8325072:T:A	N654I	0.986
19:8325073:T:A	N654Y	0.986
19:8324670:A:C	L748R	0.985
19:8333025:A:T	L642H	0.985
19:8333186:G:C	S588R	0.985

dbSNP variants (sampled 300 via entrez): RS1000083916 (19:8339862 G>A), RS1000135896 (19:8329678 G>A,C), RS1000418774 (19:8329039 C>T), RS1000538845 (19:8341257 G>A,C), RS1000591301 (19:8341502 C>G), RS1000635726 (19:8330308 T>A), RS1000648099 (19:8334412 G>A,C), RS1000691675 (19:8324203 C>A,T), RS1000769271 (19:8334639 C>A,G,T), RS1000873248 (19:8335199 G>A,T), RS1001315486 (19:8335382 G>A,C,T), RS1001371998 (19:8336875 G>C), RS1001425611 (19:8325718 T>C), RS1001545156 (19:8342572 G>A,C), RS1001596080 (19:8342777 T>A)

Disease associations

OMIM: gene MIM:614611 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006627_35	Diastolic blood pressure	5.000000e-12
GCST90002385_308	High light scatter reticulocyte count	1.000000e-09
GCST90002386_57	High light scatter reticulocyte percentage of red cells	4.000000e-10
GCST90002405_577	Reticulocyte count	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects expression	4
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
Aflatoxin B1	increases expression	2
GSK-J4	decreases expression	1
bisphenol A	decreases expression	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Estradiol	affects cotreatment, increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
N-Nitrosopyrrolidine	increases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	increases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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