INKA1

Summary

INKA1 (inka box actin regulator 1, HGNC:32480) is a protein-coding gene on chromosome 3p21.31, encoding PAK4-inhibitor INKA1 (Q96EL1). Inhibitor of the serine/threonine-protein kinase PAK4.

Enables protein kinase binding activity and protein serine/threonine kinase inhibitor activity. Predicted to act upstream of or within neural tube development. Located in cytoplasm and nucleus.

Source: NCBI Gene 389119 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_203370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32480
Approved symbol	INKA1
Name	inka box actin regulator 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185614
Ensembl biotype	protein_coding
OMIM	620426
Entrez	389119

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000333323, ENST00000893014

RefSeq mRNA: 2 — MANE Select: NM_203370 NM_001366281, NM_203370

CCDS: CCDS2804

Canonical transcript exons

ENST00000333323 — 2 exons

Exon	Start	End
ENSE00001291707	49803261	49803443
ENSE00001311824	49804181	49805030

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 89.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.7436 / max 55.5205, expressed in 939 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36661	2.7436	939

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	89.75	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.26	gold quality
skin of leg	UBERON:0001511	85.39	gold quality
skin of abdomen	UBERON:0001416	85.25	gold quality
zone of skin	UBERON:0000014	84.14	gold quality
esophagus mucosa	UBERON:0002469	83.84	gold quality
lower esophagus mucosa	UBERON:0035834	83.58	gold quality
gingiva	UBERON:0001828	81.98	gold quality
apex of heart	UBERON:0002098	81.66	gold quality
epithelial cell of pancreas	CL:0000083	81.37	gold quality
gingival epithelium	UBERON:0001949	81.30	gold quality
cortical plate	UBERON:0005343	80.83	gold quality
right coronary artery	UBERON:0001625	80.24	gold quality
mammalian vulva	UBERON:0000997	79.67	gold quality
descending thoracic aorta	UBERON:0002345	79.67	gold quality
left ventricle myocardium	UBERON:0006566	79.67	gold quality
cardiac muscle of right atrium	UBERON:0003379	79.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.54	gold quality
thoracic aorta	UBERON:0001515	79.22	gold quality
ascending aorta	UBERON:0001496	79.13	gold quality
vastus lateralis	UBERON:0001379	78.93	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.19	gold quality
kidney epithelium	UBERON:0004819	78.14	gold quality
aorta	UBERON:0000947	78.05	gold quality
oocyte	CL:0000023	77.99	gold quality
monocyte	CL:0000576	77.96	gold quality
esophagus squamous epithelium	UBERON:0006920	77.94	gold quality
sperm	CL:0000019	77.89	gold quality
esophagus	UBERON:0001043	77.79	gold quality
substantia nigra pars compacta	UBERON:0001965	77.74	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	33.91
E-MTAB-9388	yes	11.50
E-ANND-3	yes	6.63

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Inka1 is an endogenous inhibitor of PAK4 that binds to the catalytic domain and forms crystals with PAK4 in cells. (PMID:26607847)
• A competitive in vivo gain-of-function screen identifies C3orf54/INKA1 as a gene regulating leukemia stem cells (LSCs) repopulation kinetics. INKA1 overexpression stalls LSC transiently in G0 without abolishing regenerative potential; silencing has the opposite effect. (PMID:30796022)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	inka1a	ENSDARG00000070360
danio_rerio	inka1b	ENSDARG00000070404
mus_musculus	Inka1	ENSMUSG00000042106
rattus_norvegicus	Inka1	ENSRNOG00000019363

Paralogs (1): INKA2 (ENSG00000197852)

Protein

Protein identifiers

PAK4-inhibitor INKA1 — Q96EL1 (reviewed: Q96EL1)

Alternative names: Induced in neural crest by AP2-alpha protein homolog, Inka-box actin regulator 1

All UniProt accessions (1): A0A499FIG1

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of the serine/threonine-protein kinase PAK4. Acts by binding PAK4 in a substrate-like manner, inhibiting the protein kinase activity.

Subunit / interactions. Interacts with PAK4.

Subcellular location. Nucleus. Cytoplasm.

Domain organisation. Contains 2 Inka boxes (also named iBox or inca box). The Inka boxes bind and inhibit PAK4 by binding a substrate-like manner.

Similarity. Belongs to the INKA family.

RefSeq proteins (2): NP_001353210, NP_976248* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029267	FAM212	Domain
IPR039201	Inka	Family

Pfam: PF15342

UniProt features (9 total): region of interest 4, compositionally biased region 2, chain 1, strand 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4XBU	X-RAY DIFFRACTION	2.06
4XBR	X-RAY DIFFRACTION	2.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EL1-F1	58.17	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 78 (showing top): BENPORATH_ES_WITH_H3K27ME3, TAL1ALPHAE47_01, CAGCTG_AP4_Q5, CCANNAGRKGGC_UNKNOWN, HAMAI_APOPTOSIS_VIA_TRAIL_DN, RNCTGNYNRNCTGNY_UNKNOWN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_RED_DN, GOMF_PROTEIN_SERINE_THREONINE_KINASE_INHIBITOR_ACTIVITY, HEB_Q6, GOMF_ENZYME_INHIBITOR_ACTIVITY, MZF1_01, GOMF_ENZYME_REGULATOR_ACTIVITY, GOMF_KINASE_BINDING, P53_02, TAL1BETAITF2_01

GO Biological Process (1): neural tube development (GO:0021915)

GO Molecular Function (2): protein kinase binding (GO:0019901), protein serine/threonine kinase inhibitor activity (GO:0030291)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nervous system development	1
tube development	1
chordate embryonic development	1
epithelium development	1
kinase binding	1
protein serine/threonine kinase activity	1
protein kinase inhibitor activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

432 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INKA1	PAK4	O96013	826
INKA1	MGAT5B	Q3V5L5	472
INKA1	SCEL	O95171	454
INKA1	SIRT1	Q96EB6	417
INKA1	CIAO2B	Q9Y3D0	406
INKA1	TMPPE	Q6ZT21	400
INKA1	RBM6	P78332	397
INKA1	LYSMD4	Q5XG99	397
INKA1	CALHM4	Q5JW98	393
INKA1	RNF123	Q5XPI4	392
INKA1	PAK5	Q9P286	380
INKA1	SUOX	P51687	371
INKA1	CTPS2	Q9NRF8	365
INKA1	FAM98A	Q8NCA5	363
INKA1	BPIFC	Q8NFQ6	354

IntAct

41 interactions, top by confidence:

A	B	Type	Score
PAK5	INKA1	psi-mi:“MI:0915”(physical association)	0.700
INKA1	PAK5	psi-mi:“MI:0915”(physical association)	0.700
PAK4	INKA1	psi-mi:“MI:0915”(physical association)	0.670
INKA1	AIRIM	psi-mi:“MI:0915”(physical association)	0.560
ZNF417	INKA1	psi-mi:“MI:0915”(physical association)	0.560
GPANK1	INKA1	psi-mi:“MI:0915”(physical association)	0.560
DDX6	INKA1	psi-mi:“MI:0915”(physical association)	0.560
INKA1	KIF9	psi-mi:“MI:0915”(physical association)	0.560
DMWD	INKA1	psi-mi:“MI:0915”(physical association)	0.560
LMNA	INKA1	psi-mi:“MI:0915”(physical association)	0.560
INKA1	PEX7	psi-mi:“MI:0915”(physical association)	0.560
INKA1	BSCL2	psi-mi:“MI:0915”(physical association)	0.560
INKA1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
PEX7	INKA1	psi-mi:“MI:0915”(physical association)	0.400
INKA1	SDCBP	psi-mi:“MI:0914”(association)	0.350
PAK4	INKA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): FAM212A (Two-hybrid), FAM212A (Two-hybrid), FAM212A (Two-hybrid), FAM212A (Two-hybrid), FAM212A (Two-hybrid), FAM212A (Two-hybrid), GPANK1 (Two-hybrid), FAM212A (Two-hybrid), FAM212A (Two-hybrid), PAK4 (Affinity Capture-MS), BTRC (Affinity Capture-MS), FBXW11 (Affinity Capture-MS), WDR6 (Affinity Capture-MS), TTC19 (Affinity Capture-MS), CPVL (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PPE3, A0A2R8Y2Y2, A0A494C0N9, A0A494C0Y3, A0A7I2V3R4, A0JNN8, A2VDX9, A5A769, A5PJP1, A6QPM6, A8MTW9, C9JTQ0, O15370, O35182, O43541, O70218, O75474, O89113, O94850, P0C7X2, P0DPE3, P28283, P37318, P37319, P70339, Q04890, Q10586, Q32PF6, Q5BLP8, Q5T230, Q5U5M8, Q5VY09, Q60925, Q6IQX8, Q6NZ36, Q6NZY7, Q6QNY0, Q6ZSJ8, Q7TNS8, Q80WY3

Diamond homologs: A0FGR0, A6QP24, A7LKB2, F1QPR4, F1QR98, Q80VY2, Q96EL1, Q9CX62, Q9NTI7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

355 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49803360:GCTA:G	donor_gain	0.9700
3:49803364:G:GG	donor_gain	0.9500
3:49804179:A:AG	acceptor_gain	0.9000
3:49804180:G:GG	acceptor_gain	0.9000
3:49804180:GTTGT:G	acceptor_gain	0.8900
3:49803285:C:T	donor_gain	0.8800
3:49804180:GTT:G	acceptor_gain	0.8800
3:49803370:T:A	donor_gain	0.8400
3:49803439:AACTG:A	donor_loss	0.8300
3:49803444:GTGAG:G	donor_loss	0.8300
3:49803446:GAG:G	donor_loss	0.8300
3:49803444:G:GG	donor_gain	0.8200
3:49803349:TTCC:T	donor_gain	0.8000
3:49803447:AGGCT:A	donor_loss	0.8000
3:49803468:T:A	donor_gain	0.7900
3:49804137:TGAC:T	donor_gain	0.7800
3:49803624:C:G	donor_gain	0.7500
3:49803679:A:T	donor_gain	0.7500
3:49803687:G:GT	donor_gain	0.7300
3:49803635:A:G	donor_gain	0.7200
3:49803363:A:AG	donor_gain	0.7100
3:49803448:G:C	donor_loss	0.7100
3:49803674:G:GT	donor_gain	0.7100
3:49804448:G:GT	donor_gain	0.7100
3:49803294:GC:G	donor_gain	0.6700
3:49804227:A:AG	acceptor_gain	0.6400
3:49804228:G:GG	acceptor_gain	0.6400
3:49803675:G:T	donor_gain	0.6300
3:49804125:G:A	acceptor_gain	0.6300
3:49804092:GCC:G	donor_gain	0.6200

AlphaMissense

1827 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49804701:T:C	F193S	0.997
3:49804721:T:A	W200R	0.996
3:49804721:T:C	W200R	0.996
3:49804723:G:C	W200C	0.996
3:49804723:G:T	W200C	0.996
3:49804692:A:T	D190V	0.995
3:49804701:T:G	F193C	0.995
3:49804710:T:C	L196S	0.995
3:49804692:A:C	D190A	0.991
3:49804639:G:C	W172C	0.990
3:49804639:G:T	W172C	0.990
3:49804696:T:A	N191K	0.990
3:49804696:T:G	N191K	0.990
3:49804700:T:C	F193L	0.990
3:49804702:T:A	F193L	0.990
3:49804702:T:G	F193L	0.990
3:49804689:G:T	G189V	0.989
3:49804637:T:A	W172R	0.986
3:49804637:T:C	W172R	0.986
3:49804691:G:C	D190H	0.986
3:49804704:C:A	A194D	0.986
3:49804415:T:C	F98L	0.984
3:49804417:C:A	F98L	0.984
3:49804417:C:G	F98L	0.984
3:49804686:T:A	L188Q	0.983
3:49804689:G:A	G189E	0.982
3:49804692:A:G	D190G	0.982
3:49804722:G:C	W200S	0.981
3:49804707:A:T	D195V	0.980
3:49804710:T:G	L196W	0.978

dbSNP variants (sampled 300 via entrez): RS1001005784 (3:49802427 G>T), RS1001071331 (3:49804000 C>A), RS1001670157 (3:49805049 C>T), RS1002119886 (3:49803386 C>T), RS1002407139 (3:49803574 G>A,C), RS1003580213 (3:49802532 C>A,T), RS1003850933 (3:49802221 T>A), RS1004295203 (3:49803171 A>C,G), RS1004732433 (3:49802939 G>C,T), RS1005037370 (3:49801802 C>G), RS1005329548 (3:49804058 G>C), RS1005706625 (3:49804418 T>C,G), RS1005882243 (3:49803207 C>G,T), RS1005934686 (3:49803344 C>T), RS1007440367 (3:49803013 G>A)

Disease associations

OMIM: gene MIM:620426 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST003818_48	Resting heart rate	3.000000e-13
GCST005951_49	Body mass index	1.000000e-08
GCST006920_7	Regular attendance at a gym or sports club	6.000000e-10
GCST006922_9	Regular attendance at a religious group	3.000000e-08
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST010002_422	Refractive error	4.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009592	social interaction measurement
EFO:0004337	intelligence
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases expression	2
Cadmium Chloride	decreases expression	2
sotorasib	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
licochalcone B	increases expression	1
jinfukang	increases expression, affects cotreatment	1
trametinib	increases expression, affects cotreatment	1
NVP-BKM120	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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