KRTAP2-2

Summary

KRTAP2-2 (keratin associated protein 2-2, HGNC:18905) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 2-2 (Q9BYT5). In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-link….

Predicted to be located in cytosol.

Source: NCBI Gene 728279 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_033032

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18905
Approved symbol	KRTAP2-2
Name	keratin associated protein 2-2
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP2.2
Ensembl gene	ENSG00000214518
Ensembl biotype	protein_coding
Entrez	728279

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000398477

RefSeq mRNA: 1 — MANE Select: NM_033032 NM_033032

CCDS: CCDS54122

Canonical transcript exons

ENST00000398477 — 1 exons

Exon	Start	End
ENSE00001533294	41054498	41055230

Expression profiles

Bgee: expression breadth broad, 35 present calls, max score 42.16.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1670 / max 22.1598, expressed in 71 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165868	0.1116	43
165869	0.0554	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	42.16	gold quality
zone of skin	UBERON:0000014	39.95	gold quality
right lung	UBERON:0002167	39.81	gold quality
skin of leg	UBERON:0001511	38.62	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
liver	UBERON:0002107	31.05	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
right lobe of liver	UBERON:0001114	29.56	gold quality
prefrontal cortex	UBERON:0000451	29.21	gold quality
blood	UBERON:0000178	29.16	gold quality
muscle of leg	UBERON:0001383	28.92	gold quality
tonsil	UBERON:0002372	28.90	gold quality
gastrocnemius	UBERON:0001388	28.60	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
heart left ventricle	UBERON:0002084	26.65	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
leukocyte	CL:0000738	26.20	gold quality
monocyte	CL:0000576	26.06	gold quality
pancreas	UBERON:0001264	26.06	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting KRTAP2-2, 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-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-9851-5P	97.57	67.49	1067
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-610	96.84	67.98	905
HSA-MIR-4652-5P	96.46	64.22	553

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap5-2	ENSMUSG00000054759
mus_musculus	Krtap5-20	ENSMUSG00000056885
mus_musculus	Krtap5-26	ENSMUSG00000109859
mus_musculus	Krtap5-24	ENSMUSG00000110324
rattus_norvegicus	Krtap5-8	ENSRNOG00000020131
rattus_norvegicus	AABR07006049.1	ENSRNOG00000046649

Paralogs (47): KRTAP4-4 (ENSG00000171396), KRTAP9-7 (ENSG00000180386), KRTAP5-5 (ENSG00000185940), KRTAP12-1 (ENSG00000187175), KRTAP9-8 (ENSG00000187272), KRTAP10-8 (ENSG00000187766), KRTAP10-6 (ENSG00000188155), KRTAP1-1 (ENSG00000188581), KRTAP10-12 (ENSG00000189169), KRTAP4-3 (ENSG00000196156), KRTAP9-9 (ENSG00000198083), KRTAP4-6 (ENSG00000198090), KRTAP4-5 (ENSG00000198271), KRTAP4-1 (ENSG00000198443), KRTAP9-3 (ENSG00000204873), KRTAP4-8 (ENSG00000204880), KRTAP1-4 (ENSG00000204887), KRTAP12-3 (ENSG00000205439), KRTAP10-2 (ENSG00000205445), KRTAP5-6 (ENSG00000205864), KRTAP5-2 (ENSG00000205867), KRTAP16-1 (ENSG00000212657), KRTAP9-6 (ENSG00000212659), KRTAP4-11 (ENSG00000212721), KRTAP4-9 (ENSG00000212722), KRTAP2-3 (ENSG00000212724), KRTAP2-1 (ENSG00000212725), KRTAP10-3 (ENSG00000212935), KRTAP4-12 (ENSG00000213416), KRTAP2-4 (ENSG00000213417), KRTAP10-4 (ENSG00000215454), KRTAP10-1 (ENSG00000215455), KRTAP10-9 (ENSG00000221837), KRTAP1-5 (ENSG00000221852), KRTAP10-10 (ENSG00000221859), KRTAP12-2 (ENSG00000221864), KRTAP1-3 (ENSG00000221880), KRTAP9-2 (ENSG00000239886), KRTAP9-1 (ENSG00000240542), KRTAP4-7 (ENSG00000240871)

Protein

Protein identifiers

Keratin-associated protein 2-2 — Q9BYT5 (reviewed: Q9BYT5)

Alternative names: High sulfur keratin-associated protein 2.2, Keratin-associated protein 2.2

All UniProt accessions (1): Q9BYT5

UniProt curated annotations — full annotation on UniProt →

Function. In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.

Subunit / interactions. Interacts with hair keratins.

Similarity. Belongs to the KRTAP type 2 family.

RefSeq proteins (1): NP_149021* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family
IPR052154	KRTAP_type_2-like	Family

Pfam: PF01500

UniProt features (3 total): chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYT5-F1	33.11	0.00

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 5 (showing top): REACTOME_KERATINIZATION, MIR3619_5P, MIR4709_3P, chr17q21, ZHOU_INFLAMMATORY_RESPONSE_LPS_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): cytosol (GO:0005829), keratin filament (GO:0045095), intermediate filament (GO:0005882)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP2-2	TBC1D3K	A0A087X1G2	590
KRTAP2-2	KRTAP22-1	Q3MIV0	580
KRTAP2-2	KRTAP8-1	Q8IUC2	518
KRTAP2-2	KRTAP13-3	Q3SY46	518
KRTAP2-2	TBC1D3H	P0C7X1	512
KRTAP2-2	ARHGEF33	A8MVX0	507
KRTAP2-2	KRTAP6-1	Q3LI64	505
KRTAP2-2	KRTAP21-2	Q3LI59	505
KRTAP2-2	TBC1D3D	A0A087WVF3	478
KRTAP2-2	KRTAP24-1	Q3LI83	477
KRTAP2-2	FRMD1	Q8N878	468
KRTAP2-2	SPRR4	Q96PI1	447
KRTAP2-2	KRTAP4-3	Q9BYR4	447
KRTAP2-2	KRTAP3-2	Q9BYR7	447
KRTAP2-2	KRTAP1-1	Q07627	446

IntAct

0 interactions, top by confidence:

BioGRID (3): KRTAP2-2 (Negative Genetic), KRTAP2-2 (Affinity Capture-MS), KRTAP2-2 (Affinity Capture-MS)

ESM2 similar proteins: A5A6P5, A6QP35, A8MTY7, A8MVA2, A8MXZ3, O75690, P02438, P02441, P02442, P02443, P08131, P0C7H8, P26371, P59990, P59991, P60014, P60331, P60368, P60369, P60370, P60371, P60372, P60409, P60410, P60411, P60412, P60413, Q05B44, Q07627, Q3V2C1, Q6L8G4, Q6L8G8, Q6L8G9, Q6L8H2, Q701N4, Q8IUG1, Q9BQ66, Q9BYP9, Q9BYQ0, Q9BYQ2

Diamond homologs: P02441, P02442, P02443, P0C7H8, Q9BYR9, Q9BYT5, Q9BYU5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

163 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41055000:T:A	donor_gain	0.9100
17:41055170:G:C	donor_gain	0.7500
17:41055025:A:T	donor_gain	0.6600
17:41055163:C:A	donor_gain	0.6600
17:41054854:T:TA	donor_gain	0.6500
17:41054950:C:CT	donor_gain	0.6400
17:41054898:TG:T	donor_gain	0.6100
17:41055029:C:CT	donor_gain	0.5900
17:41054843:G:C	donor_gain	0.5800
17:41054947:A:T	donor_gain	0.5800
17:41055030:G:T	donor_gain	0.5700
17:41055026:C:T	donor_gain	0.5600
17:41055162:C:A	donor_gain	0.5600
17:41054524:T:TC	acceptor_gain	0.5500
17:41054687:C:CA	donor_gain	0.5300
17:41054808:TG:T	donor_gain	0.5300
17:41054563:T:TA	donor_gain	0.5100
17:41054584:T:C	donor_gain	0.5100
17:41054764:T:TA	donor_gain	0.5100
17:41054944:TGCAC:T	donor_gain	0.5000
17:41054521:T:C	acceptor_gain	0.4900
17:41055174:A:AC	donor_gain	0.4900
17:41054753:G:C	donor_gain	0.4700
17:41055001:C:A	donor_gain	0.4500
17:41054515:T:TC	acceptor_gain	0.4400
17:41054521:T:TC	acceptor_gain	0.4300
17:41054583:AT:A	donor_gain	0.4300
17:41054524:T:C	acceptor_gain	0.4200
17:41054654:T:TA	donor_gain	0.4200
17:41054948:C:T	donor_gain	0.4200

AlphaMissense

783 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41054947:A:G	C89R	0.936
17:41054930:C:A	W94C	0.926
17:41054930:C:G	W94C	0.926
17:41054977:A:G	C79R	0.922
17:41054945:G:C	C89W	0.910
17:41054982:A:G	I77T	0.901
17:41054982:A:C	I77S	0.898
17:41054982:A:T	I77N	0.888
17:41054975:G:C	C79W	0.885
17:41054946:C:T	C89Y	0.881
17:41054962:A:G	C84R	0.876
17:41054946:C:G	C89S	0.872
17:41054947:A:T	C89S	0.872
17:41055099:G:A	T38I	0.872
17:41054932:A:G	W94R	0.865
17:41054932:A:T	W94R	0.865
17:41054972:G:C	C80W	0.862
17:41054995:A:G	C73R	0.850
17:41054933:G:C	C93W	0.846
17:41054976:C:T	C79Y	0.845
17:41054936:G:C	C92W	0.843
17:41054935:A:G	C93R	0.841
17:41054960:G:C	C84W	0.839
17:41054998:C:G	G72R	0.827
17:41055088:G:T	R42S	0.817
17:41054976:C:G	C79S	0.815
17:41054977:A:T	C79S	0.815
17:41054993:G:C	C73W	0.814
17:41055011:G:C	C67W	0.813
17:41055023:G:C	C63W	0.806

dbSNP variants (sampled 300 via entrez): RS1001235895 (17:41054541 T>A,C,G), RS1002352905 (17:41054262 T>A), RS1002904641 (17:41056250 A>C), RS1003560410 (17:41054144 G>A,T), RS1004959534 (17:41055596 A>C,G), RS1006380706 (17:41055233 G>A,C), RS1008925501 (17:41054598 G>C), RS1009631008 (17:41056307 G>A), RS1009705958 (17:41056504 C>A,G,T), RS1011034652 (17:41054558 T>C), RS1011440190 (17:41056395 G>A,T), RS1011520998 (17:41054784 G>T), RS1011747338 (17:41056884 A>C,G), RS1011803350 (17:41056261 C>G,T), RS1012168389 (17:41054155 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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
mancozeb	decreases expression	1
Arsenic	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Formaldehyde	decreases expression	1
Rotenone	increases expression	1
Smoke	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Genistein	decreases expression	1

Clinical trials (associated diseases)

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