INKA2

Summary

INKA2 (inka box actin regulator 2, HGNC:28045) is a protein-coding gene on chromosome 1p13.2, encoding PAK4-inhibitor INKA2 (Q9NTI7). Inhibitor of the serine/threonine-protein kinase PAK4.

Enables protein kinase binding activity. Located in nucleolus and nucleoplasm.

Source: NCBI Gene 55924 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_019099

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28045
Approved symbol	INKA2
Name	inka box actin regulator 2
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31105
Ensembl gene	ENSG00000197852
Ensembl biotype	protein_coding
OMIM	620403
Entrez	55924

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000357260, ENST00000444059, ENST00000527570, ENST00000527621, ENST00000534365

RefSeq mRNA: 2 — MANE Select: NM_019099 NM_019099, NM_198926

CCDS: CCDS841

Canonical transcript exons

ENST00000357260 — 2 exons

Exon	Start	End
ENSE00002156876	111739186	111739395
ENSE00003846721	111722064	111727804

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 89.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0966 / max 225.8786, expressed in 1462 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13841	6.0966	1462

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	89.22	gold quality
apex of heart	UBERON:0002098	85.86	gold quality
prefrontal cortex	UBERON:0000451	84.23	gold quality
heart left ventricle	UBERON:0002084	83.33	gold quality
right frontal lobe	UBERON:0002810	83.25	gold quality
cardiac ventricle	UBERON:0002082	83.15	gold quality
tendon of biceps brachii	UBERON:0008188	82.61	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	82.46	gold quality
frontal cortex	UBERON:0001870	82.31	gold quality
monocyte	CL:0000576	82.13	gold quality
mononuclear cell	CL:0000842	82.04	gold quality
cingulate cortex	UBERON:0003027	82.04	gold quality
anterior cingulate cortex	UBERON:0009835	82.02	gold quality
leukocyte	CL:0000738	81.99	gold quality
stromal cell of endometrium	CL:0002255	81.93	gold quality
neocortex	UBERON:0001950	81.62	gold quality
cervix squamous epithelium	UBERON:0006922	81.42	gold quality
right atrium auricular region	UBERON:0006631	80.93	gold quality
cardiac atrium	UBERON:0002081	80.88	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.88	gold quality
type B pancreatic cell	CL:0000169	80.83	gold quality
olfactory bulb	UBERON:0002264	80.69	gold quality
cerebral cortex	UBERON:0000956	80.64	gold quality
heart	UBERON:0000948	80.55	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.40	gold quality
myocardium	UBERON:0002349	80.31	silver quality
cardiac muscle of right atrium	UBERON:0003379	80.27	silver quality
tongue squamous epithelium	UBERON:0006919	80.12	gold quality
cerebellar vermis	UBERON:0004720	79.96	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	79.77	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-8060	no	46.84
E-ANND-3	no	3.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

173 targeting INKA2, 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-8485	100.00	77.57	4731
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-1321	99.84	65.30	1811

Literature-anchored findings (GeneRIF, showing 1)

• Fra-2/AP-1 regulates melanoma cell metastasis by downregulating Fam212b. (PMID:33188281)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	inka2	ENSDARG00000073900
mus_musculus	Inka2	ENSMUSG00000048458
rattus_norvegicus	Inka2	ENSRNOG00000015691

Paralogs (1): INKA1 (ENSG00000185614)

Protein

Protein identifiers

PAK4-inhibitor INKA2 — Q9NTI7 (reviewed: Q9NTI7)

Alternative names: Induced in neural crest by AP2-alpha protein-related homolog, Inka-box actin regulator 2

All UniProt accessions (3): E9PND8, E9PR53, Q9NTI7

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.

Domain organisation. The Inka box (also named iBox or inca box) binds and inhibits PAK4 by binding a substrate-like manner.

Similarity. Belongs to the INKA family.

RefSeq proteins (2): NP_061972, NP_945120 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029267	FAM212	Domain
IPR039201	Inka	Family

Pfam: PF15342

UniProt features (7 total): region of interest 4, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NTI7-F1	62.39	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): SHEPARD_BMYB_MORPHOLINO_DN, CORRE_MULTIPLE_MYELOMA_UP, IK3_01, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, SHEPARD_BMYB_TARGETS, SHEN_SMARCA2_TARGETS_DN, GRYDER_PAX3FOXO1_TOP_ENHANCERS, TAATTA_CHX10_01, GOCC_NUCLEOLUS, GOMF_PROTEIN_SERINE_THREONINE_KINASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOMF_KINASE_BINDING, KOYAMA_SEMA3B_TARGETS_DN, MARTENS_BOUND_BY_PML_RARA_FUSION

GO Biological Process (0):

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

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
kinase binding	1
protein serine/threonine kinase activity	1
protein kinase inhibitor activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

324 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INKA2	CLMP	Q9H6B4	519
INKA2	PAK4	O96013	437
INKA2	C2orf80	Q0P641	395
INKA2	PHLDA3	Q9Y5J5	391
INKA2	CDH5	P33151	390
INKA2	KLHDC7A	Q5VTJ3	364
INKA2	GDF15	P78360	353
INKA2	UBALD2	Q8IYN6	348
INKA2	PROS1	P07225	347
INKA2	EDA2R	Q9HAV5	337
INKA2	BUD13	Q9BRD0	329
INKA2	TIGD1	Q96MW7	325
INKA2	TMEM169	Q96HH4	321
INKA2	SESN2	P58004	320
INKA2	TFIP11	Q9UBB9	318

IntAct

3 interactions, top by confidence:

A	B	Type	Score
INKA2	CDC42BPA	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): FAM212B (Affinity Capture-RNA), FAM212B (Affinity Capture-RNA), DNASE1L2 (Affinity Capture-MS), NOSIP (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), CDC42BPA (Affinity Capture-MS), CEP128 (Affinity Capture-MS), CEP128 (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), DNASE1L2 (Affinity Capture-MS), CDC42BPA (Affinity Capture-MS), FAM212B (Affinity Capture-RNA), FAM212B (Biochemical Activity), FAM212B (Affinity Capture-RNA), POLL (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVZ6, A5D7I0, A6H7B4, A6NDZ8, A6NE82, A6NJ08, A6NJB7, A6NJI1, A6NL46, A6QP24, A8MUA0, A8MUI8, A8MV72, A8MX80, B2RW88, O94850, P0C6A0, P24097, P50617, Q0P5M0, Q0VD86, Q2KIL8, Q3B8N5, Q3SY00, Q3SYA9, Q3UN58, Q5BMD4, Q5JTZ5, Q5RBE4, Q5VZ46, Q66MI6, Q68US1, Q6GQV0, Q6PAC4, Q80TS7, Q80VY2, Q8BFY7, Q8BII1, Q8IXW0, Q8K2F3

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1396 predictions. Top by Δscore:

Variant	Effect	Δscore
1:111691330:TCAG:T	acceptor_loss	1.0000
1:111691331:CA:C	acceptor_loss	1.0000
1:111691332:A:AG	acceptor_gain	1.0000
1:111691332:AGATC:A	acceptor_gain	1.0000
1:111691333:G:GT	acceptor_gain	1.0000
1:111691333:GA:G	acceptor_gain	1.0000
1:111691333:GAT:G	acceptor_gain	1.0000
1:111691333:GATC:G	acceptor_gain	1.0000
1:111691333:GATCG:G	acceptor_gain	1.0000
1:111691415:CTGG:C	donor_loss	1.0000
1:111691417:GGTA:G	donor_loss	1.0000
1:111691418:G:A	donor_loss	1.0000
1:111691418:G:GG	donor_gain	1.0000
1:111691419:TAA:T	donor_loss	1.0000
1:111695339:A:AG	acceptor_gain	1.0000
1:111695340:G:GG	acceptor_gain	1.0000
1:111695340:GAC:G	acceptor_gain	1.0000
1:111695340:GACA:G	acceptor_gain	1.0000
1:111695406:AAAGG:A	donor_loss	1.0000
1:111695407:AAGGT:A	donor_loss	1.0000
1:111695408:AGG:A	donor_loss	1.0000
1:111695409:GGT:G	donor_loss	1.0000
1:111695410:G:T	donor_loss	1.0000
1:111695411:T:A	donor_loss	1.0000
1:111697440:GCAA:G	acceptor_gain	1.0000
1:111697493:GGACA:G	donor_gain	1.0000
1:111697494:G:T	donor_gain	1.0000
1:111697494:GACA:G	donor_gain	1.0000
1:111697494:GACAG:G	donor_gain	1.0000
1:111697498:G:GG	donor_gain	1.0000

AlphaMissense

1930 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:111727357:A:G	W169R	0.999
1:111727357:A:T	W169R	0.999
1:111727368:A:G	L165P	0.998
1:111727734:A:G	L43P	0.998
1:111726976:A:G	W296R	0.997
1:111726976:A:T	W296R	0.997
1:111727355:C:A	W169C	0.997
1:111727355:C:G	W169C	0.997
1:111727441:A:G	W141R	0.997
1:111727441:A:T	W141R	0.997
1:111726978:A:T	V295D	0.996
1:111727353:A:G	L170P	0.996
1:111727377:A:G	F162S	0.996
1:111727386:T:A	D159V	0.996
1:111727728:A:G	L45P	0.996
1:111726974:C:A	W296C	0.995
1:111726974:C:G	W296C	0.995
1:111726981:G:T	A294D	0.995
1:111727218:A:G	L215S	0.995
1:111727439:C:A	W141C	0.995
1:111727439:C:G	W141C	0.995
1:111727743:A:G	L40P	0.995
1:111727764:A:G	M33T	0.995
1:111727776:A:G	L29S	0.995
1:111739199:A:G	L15P	0.995
1:111727230:A:G	F211S	0.994
1:111727389:C:A	G158V	0.994
1:111727392:A:G	L157S	0.994
1:111727368:A:T	L165Q	0.993
1:111727386:T:G	D159A	0.993

dbSNP variants (sampled 300 via entrez): RS1000037753 (1:111757224 G>A), RS1000411220 (1:111751935 T>G), RS1000483665 (1:111744888 A>G), RS1000501124 (1:111730401 TGTC>T), RS1000511744 (1:111722507 G>T), RS1000523064 (1:111741928 CT>C), RS1000566472 (1:111730636 C>A,G,T), RS1000749368 (1:111753304 T>G), RS1000753087 (1:111745163 G>A,T), RS1000915413 (1:111740339 G>T), RS1000947 (1:111734975 T>A,C), RS1001032106 (1:111737161 C>T), RS1001078291 (1:111724877 A>G,T), RS1001153886 (1:111742024 T>C,G), RS1001230527 (1:111746476 T>C)

Disease associations

OMIM: gene MIM:620403 | 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
GCST002783_287	Body mass index	5.000000e-06
GCST003875_29	Gut microbiota (bacterial taxa)	8.000000e-09
GCST007216_8	Crohn’s disease	4.000000e-08
GCST90012857_5	Falling risk	3.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs197388	DDX20, INKA2		0.00	0

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	6
Cisplatin	affects expression, increases expression	4
Acetaminophen	increases expression	2
Aflatoxin B1	increases expression	2
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	affects splicing, increases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
Decitabine	affects expression	1
Cidofovir	increases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Cadmium	increases abundance, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Fluorouracil	affects reaction, increases expression	1
Ifosfamide	increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Quercetin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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