KRT222

Summary

KRT222 (keratin 222, HGNC:28695) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-like protein KRT222 (Q8N1A0).

Predicted to enable structural molecule activity. Predicted to be located in intermediate filament.

Source: NCBI Gene 125113 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_152349

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28695
Approved symbol	KRT222
Name	keratin 222
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KA21, MGC45562
Ensembl gene	ENSG00000213424
Ensembl biotype	protein_coding
Entrez	125113

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 nonsense_mediated_decay, 2 protein_coding

ENST00000394049, ENST00000394052, ENST00000580719, ENST00000581564, ENST00000862990

RefSeq mRNA: 1 — MANE Select: NM_152349 NM_152349

CCDS: CCDS11371

Canonical transcript exons

ENST00000394052 — 6 exons

Exon	Start	End
ENSE00001517387	40654665	40656630
ENSE00003481460	40659987	40660207
ENSE00003562649	40657352	40657487
ENSE00003592841	40665004	40665177
ENSE00003618275	40657674	40657750
ENSE00003639032	40661916	40662044

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 90.29.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8929 / max 932.9849, expressed in 253 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165782	2.8929	253

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	90.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.27	gold quality
Brodmann (1909) area 46	UBERON:0006483	86.81	gold quality
primary visual cortex	UBERON:0002436	86.56	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.05	gold quality
cerebellar cortex	UBERON:0002129	86.02	gold quality
cerebellar hemisphere	UBERON:0002245	85.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.78	gold quality
cerebellum	UBERON:0002037	85.74	gold quality
superior frontal gyrus	UBERON:0002661	84.43	gold quality
postcentral gyrus	UBERON:0002581	84.30	gold quality
prefrontal cortex	UBERON:0000451	83.87	gold quality
right frontal lobe	UBERON:0002810	83.69	gold quality
frontal cortex	UBERON:0001870	83.68	gold quality
occipital lobe	UBERON:0002021	83.60	gold quality
anterior cingulate cortex	UBERON:0009835	83.38	gold quality
parietal lobe	UBERON:0001872	83.22	gold quality
neocortex	UBERON:0001950	82.95	gold quality
entorhinal cortex	UBERON:0002728	82.81	gold quality
cerebral cortex	UBERON:0000956	82.43	gold quality
nucleus accumbens	UBERON:0001882	82.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.56	gold quality
caudate nucleus	UBERON:0001873	80.69	gold quality
cerebellar vermis	UBERON:0004720	80.23	gold quality
putamen	UBERON:0001874	79.78	gold quality
brain	UBERON:0000955	79.75	gold quality
middle temporal gyrus	UBERON:0002771	79.72	gold quality
forebrain	UBERON:0001890	79.58	gold quality
hypothalamus	UBERON:0001898	79.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting KRT222, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
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-3613-3P	100.00	76.36	7965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	krt222	ENSDARG00000071518
mus_musculus	Krt222	ENSMUSG00000035849
rattus_norvegicus	Krt222	ENSRNOG00000010839

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360)

Protein

Protein identifiers

Keratin-like protein KRT222 — Q8N1A0 (reviewed: Q8N1A0)

Alternative names: Keratin-222, Keratin-222 pseudogene

All UniProt accessions (2): Q8N1A0, J3QQR9

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the intermediate filament family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N1A0-1	1	yes
Q8N1A0-2	2

RefSeq proteins (1): NP_689562* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002957	Keratin_I	Family
IPR018039	IF_conserved	Conserved_site
IPR039008	IF_rod_dom	Domain
IPR052857	IF_Keratin-like	Family

Pfam: PF00038

UniProt features (4 total): chain 1, domain 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N1A0-F1	75.71	0.50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 99 (showing top): NKX25_02, MEF2_02, FOXD3_01, GRE_C, CTGYNNCTYTAA_UNKNOWN, ACEVEDO_LIVER_CANCER_UP, CTAWWWATA_RSRFC4_Q2, AR_01, TAATTA_CHX10_01, MEF2_03, HNF3_Q6, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, YNTTTNNNANGCARM_UNKNOWN, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, MIKKELSEN_ES_ICP_WITH_H3K4ME3

GO Biological Process (0):

GO Molecular Function (2): structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (1): intermediate filament (GO:0005882)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
molecular_function	1
binding	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

1164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT222	ZNF808	Q8N4W9	371
KRT222	MROH7	Q68CQ1	370
KRT222	TSPAN19	P0C672	364
KRT222	ANKRD34A	Q69YU3	349
KRT222	TMEM260	Q9NX78	348
KRT222	TMEM60	Q9H2L4	322
KRT222	ZNF428	Q96B54	322
KRT222	MANEAL	Q5VSG8	315
KRT222	PNMA6A	P0CW24	310
KRT222	TMEM178B	H3BS89	308
KRT222	DBNDD1	Q9H9R9	305
KRT222	ABHD1	Q96SE0	303
KRT222	TMEM35A	Q53FP2	298
KRT222	ARMCX4	Q5H9R4	298
KRT222	SLC25A48	Q6ZT89	294

IntAct

45 interactions, top by confidence:

A	B	Type	Score
HSPA6	KRT222	psi-mi:“MI:0915”(physical association)	0.560
CASP6	KRT222	psi-mi:“MI:0915”(physical association)	0.560
CCK	KRT222	psi-mi:“MI:0915”(physical association)	0.560
KRT222	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	KRT222	psi-mi:“MI:0915”(physical association)	0.560
KRT222	PEX1	psi-mi:“MI:0915”(physical association)	0.560
RAN	KRT222	psi-mi:“MI:0915”(physical association)	0.560
KRT222	ICAM5	psi-mi:“MI:0915”(physical association)	0.560
KRT222	WFS1	psi-mi:“MI:0915”(physical association)	0.560
BAG6	KRT222	psi-mi:“MI:0915”(physical association)	0.560
KLF11	KRT222	psi-mi:“MI:0915”(physical association)	0.560
KIF1B	KRT222	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (37): KRT222 (Affinity Capture-MS), KRT222 (Two-hybrid), KRT222 (Proximity Label-MS), KRT222 (Affinity Capture-MS), CEP152 (Affinity Capture-MS), NEFM (Affinity Capture-MS), GNMT (Affinity Capture-MS), PRPF19 (Affinity Capture-MS), RUFY3 (Affinity Capture-MS), ATG16L1 (Affinity Capture-MS), BCAS2 (Affinity Capture-MS), CEP164 (Affinity Capture-MS), PLEC (Affinity Capture-MS), CEP63 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS)

ESM2 similar proteins: A2AMT1, A2ARZ3, A4FU69, A6NNP5, A8DYP0, E9QMW4, O15061, O35668, O43491, O70318, P08553, P0DMS1, P12839, P54256, P97434, Q02435, Q02645, Q06002, Q06637, Q0VF96, Q12934, Q29KL8, Q2KI75, Q2MJV9, Q2TA00, Q3MHH7, Q4KM62, Q5MY90, Q5R6R3, Q5TF21, Q5ZM60, Q6DJR2, Q6NZL0, Q6P6L0, Q70IV5, Q7Z7B0, Q7ZX27, Q80Y56, Q8CCX5, Q8IWF9

Diamond homologs: P08552, P19012, Q04948, Q2KI75, Q61414, Q6IFV3, Q7SYF8, Q7ZTS4, Q8CCX5, Q8N1A0, A5A6M5, A5A6P3, B0LKP1, O76009, O76011, P02534, P25690, Q07427, Q0P5J7, Q14525, Q15323, Q3TRJ4, Q61765, Q61897, Q8K0Y2, Q9D646, A6QQJ3, O57611, P02544, P15331, P20152, P21807, P23729, P31000, P31393, P35617, P41219, P48670, P48674, Q5R1W8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

810 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40657350:A:AC	donor_gain	1.0000
17:40657351:C:CA	donor_gain	1.0000
17:40657351:C:CC	donor_gain	1.0000
17:40657488:C:CC	acceptor_gain	1.0000
17:40657669:CTCA:C	donor_loss	1.0000
17:40657670:TCACC:T	donor_loss	1.0000
17:40657671:CACCT:C	donor_loss	1.0000
17:40657672:A:T	donor_loss	1.0000
17:40657673:C:T	donor_loss	1.0000
17:40657748:TAT:T	acceptor_gain	1.0000
17:40657749:ATC:A	acceptor_loss	1.0000
17:40657749:ATCTG:A	acceptor_loss	1.0000
17:40657750:TC:T	acceptor_loss	1.0000
17:40657750:TCT:T	acceptor_loss	1.0000
17:40657751:C:CA	acceptor_loss	1.0000
17:40657751:C:CC	acceptor_gain	1.0000
17:40660203:CTTTC:C	acceptor_gain	1.0000
17:40662041:CTAG:C	acceptor_gain	1.0000
17:40662042:TAGCT:T	acceptor_loss	1.0000
17:40662043:AGCT:A	acceptor_loss	1.0000
17:40662044:GC:G	acceptor_loss	1.0000
17:40662044:GCT:G	acceptor_loss	1.0000
17:40662045:C:A	acceptor_loss	1.0000
17:40662045:C:CC	acceptor_gain	1.0000
17:40662059:A:T	acceptor_gain	1.0000
17:40656554:A:AC	donor_gain	0.9900
17:40656555:C:CC	donor_gain	0.9900
17:40656560:T:A	donor_gain	0.9900
17:40656626:CTGTC:C	acceptor_gain	0.9900
17:40656631:C:CA	acceptor_loss	0.9900

AlphaMissense

1953 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40656537:A:C	F251L	0.996
17:40656537:A:T	F251L	0.996
17:40656539:A:G	F251L	0.996
17:40656597:C:A	W231C	0.996
17:40656597:C:G	W231C	0.996
17:40656599:A:G	W231R	0.996
17:40656599:A:T	W231R	0.996
17:40660014:C:G	R140P	0.992
17:40660038:A:G	L132P	0.990
17:40661969:C:G	A58P	0.990
17:40660110:A:G	L108P	0.989
17:40656532:A:G	L253P	0.988
17:40656544:A:G	L249P	0.988
17:40656565:A:G	L242S	0.988
17:40656460:A:G	L277P	0.987
17:40661990:C:G	A51P	0.987
17:40656598:C:G	W231S	0.986
17:40661921:C:G	A74P	0.986
17:40661977:A:G	L55P	0.986
17:40656544:A:T	L249H	0.985
17:40656559:T:A	K244I	0.985
17:40660008:A:G	L142P	0.985
17:40656582:A:C	F236L	0.984
17:40656582:A:T	F236L	0.984
17:40656584:A:G	F236L	0.984
17:40656538:A:G	F251S	0.983
17:40656585:G:C	F235L	0.983
17:40656585:G:T	F235L	0.983
17:40656587:A:G	F235L	0.983
17:40660185:A:G	L83P	0.982

dbSNP variants (sampled 300 via entrez): RS1000058895 (17:40658281 C>T), RS1000127471 (17:40656433 G>A,C), RS1000849529 (17:40665210 T>C), RS1001236584 (17:40667118 C>T), RS1001453020 (17:40666157 C>A,G,T), RS1002110932 (17:40659400 C>G), RS1002433447 (17:40661545 G>C), RS1002517180 (17:40654642 GT>G,GTT), RS1002612032 (17:40654325 C>T), RS1003475231 (17:40655625 T>G), RS1003681384 (17:40662415 C>A,G,T), RS1003704310 (17:40663054 G>C), RS1003758938 (17:40655093 A>G), RS1004092604 (17:40661471 G>T), RS1004160258 (17:40662635 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003075_26	Cognitive decline rate in late mild cognitive impairment	2.000000e-07
GCST003075_59	Cognitive decline rate in late mild cognitive impairment	2.000000e-07
GCST007563_12	Allergic disease (asthma, hay fever or eczema)	2.000000e-16
GCST007564_26	Asthma or allergic disease (pleiotropy)	1.000000e-15
GCST008916_33	Asthma	3.000000e-10
GCST009798_41	Asthma	3.000000e-08
GCST009798_47	Asthma	3.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement

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	affects expression, affects cotreatment, increases expression	5
Aflatoxin B1	decreases expression, decreases methylation	2
propionaldehyde	increases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases methylation	1
Chenodeoxycholic Acid	affects cotreatment, increases expression	1
Cisplatin	decreases expression	1
Deoxycholic Acid	affects cotreatment, increases expression	1
Estradiol	decreases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, increases expression	1
Glycocholic Acid	affects cotreatment, increases expression	1
Glycodeoxycholic Acid	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Silicon Dioxide	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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