KRTAP4-4

Summary

KRTAP4-4 (keratin associated protein 4-4, HGNC:16928) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 4-4 (Q9BYR3). 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….

This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21.

Source: NCBI Gene 84616 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_032524

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16928
Approved symbol	KRTAP4-4
Name	keratin associated protein 4-4
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP4.4, KAP4.13
Ensembl gene	ENSG00000171396
Ensembl biotype	protein_coding
Entrez	84616

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000390661

RefSeq mRNA: 1 — MANE Select: NM_032524 NM_032524

CCDS: CCDS11383

Canonical transcript exons

ENST00000390661 — 1 exons

Exon	Start	End
ENSE00001508572	41159649	41160748

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 63.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0291 / max 25.2491, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165878	0.0291	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	63.09	silver quality
upper arm skin	UBERON:0004263	60.66	gold quality
epithelial cell of pancreas	CL:0000083	55.03	gold quality
tibialis anterior	UBERON:0001385	54.74	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
skin of hip	UBERON:0001554	51.95	gold quality
deltoid	UBERON:0001476	51.49	gold quality
ileal mucosa	UBERON:0000331	51.19	silver quality
upper leg skin	UBERON:0004262	51.17	silver quality
lower lobe of lung	UBERON:0008949	50.47	silver quality
myocardium	UBERON:0002349	50.25	gold quality
quadriceps femoris	UBERON:0001377	47.19	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
vastus lateralis	UBERON:0001379	45.40	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
amniotic fluid	UBERON:0000173	42.98	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
muscle tissue	UBERON:0002385	41.51	gold quality
skeletal muscle tissue	UBERON:0001134	41.46	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
cartilage tissue	UBERON:0002418	40.77	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting KRTAP4-4, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-509-3-5P	97.21	67.74	1517

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): 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), KRTAP2-2 (ENSG00000214518), 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 4-4 — Q9BYR3 (reviewed: Q9BYR3)

Alternative names: Keratin-associated protein 4-13, Keratin-associated protein 4.13, Keratin-associated protein 4.4, Ultrahigh sulfur keratin-associated protein 4.13, Ultrahigh sulfur keratin-associated protein 4.4

All UniProt accessions (1): Q9BYR3

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.

Tissue specificity. Expressed in the hair follicles.

Polymorphism. Numerous size polymorphism are present in KRTAP4 gene family, which are mainly due to variations in the sequence encoding cysteine-rich repeat segments.

Similarity. Belongs to the KRTAP type 4 family.

RefSeq proteins (1): NP_115913* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (34 total): repeat 26, sequence variant 5, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYR3-F1	38.11	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: 21 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_MOLTING_CYCLE, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, MARTENS_TRETINOIN_RESPONSE_UP, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, MIR577, MIR3619_5P, MIR214_3P, MIR761, MIR4451, MIR6501_3P

GO Biological Process (1): hair cycle (GO:0042633)

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

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
molting cycle	1
binding	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

225 interactions, top by confidence:

A	B	Type	Score
KRTAP10-8	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.600
NOTCH2NLC	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.600
CYSRT1	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.600
LCE2C	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
ZNF440	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-4	SHFL	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1E	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-4	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
ZNF497	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-4	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
AQP1	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
OTX1	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-4	NPDC1	psi-mi:“MI:0915”(physical association)	0.560
SMCP	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-5	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-4	CRCT1	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
TNS2	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-4	HEY2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (80): KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid), KRTAP4-4 (Two-hybrid)

ESM2 similar proteins: A0A286YEV6, A0A286YEX9, A0A286YEY9, A0A286YF01, A0A286YF46, A0A286YF60, A0A286YF77, A0A286YFB4, A0A286YFG1, O14633, P02438, P04459, P05687, P05688, P08131, P08175, P0DSO2, P20730, Q01642, Q01643, Q01644, Q01645, Q07627, Q3LI58, Q3LI59, Q3V2C1, Q5T750, Q5T752, Q5T754, Q5TA78, Q5TA79, Q5TA81, Q5TA82, Q5TCM9, Q8IUC1, Q8IUG1, Q9BQ66, Q9BYP8, Q9BYQ5, Q9BYQ6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	37	39.6×	2e-52
Formation of the cornified envelope	15	25.3×	2e-16

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	16	87.1×	1e-25

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

170 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41160160:T:TA	donor_gain	0.6800
17:41160090:CTG:C	donor_gain	0.6600
17:41159891:C:A	donor_gain	0.5800
17:41160237:A:T	donor_gain	0.5800
17:41160242:G:C	donor_gain	0.5600
17:41160457:CAGA:C	donor_gain	0.5600
17:41160460:A:AC	donor_gain	0.5600
17:41160461:C:CC	donor_gain	0.5600
17:41159786:CAA:C	donor_gain	0.5500
17:41159890:T:TA	donor_gain	0.5500
17:41160089:A:AC	donor_gain	0.5500
17:41160090:C:CC	donor_gain	0.5500
17:41160147:TGG:T	acceptor_gain	0.5500
17:41159963:G:GA	donor_gain	0.5400
17:41160104:A:AC	donor_gain	0.5400
17:41160105:C:CC	donor_gain	0.5400
17:41159792:ATGTT:A	donor_gain	0.5200
17:41159793:T:C	donor_gain	0.5200
17:41159969:G:C	donor_gain	0.5200
17:41159887:G:C	donor_gain	0.5100
17:41159902:G:C	donor_gain	0.5100
17:41160148:GGC:G	acceptor_gain	0.5100
17:41159901:A:AC	donor_gain	0.5000
17:41160207:TGGC:T	donor_gain	0.5000
17:41160232:TGGAC:T	donor_gain	0.5000
17:41160140:G:C	donor_gain	0.4900
17:41160225:TAGCA:T	donor_loss	0.4900
17:41160226:AGCAC:A	donor_loss	0.4900
17:41160227:GCAC:G	donor_loss	0.4900
17:41160228:CACCT:C	donor_loss	0.4900

AlphaMissense

1099 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41160560:G:C	S44R	0.606
17:41160560:G:T	S44R	0.606
17:41160562:T:G	S44R	0.606
17:41160485:G:C	S69R	0.576
17:41160485:G:T	S69R	0.576
17:41160487:T:G	S69R	0.576

dbSNP variants (sampled 300 via entrez): RS1001112921 (17:41159168 C>A), RS1001439005 (17:41159398 C>G), RS1001765574 (17:41162277 T>A), RS1001844040 (17:41160815 T>C), RS1001960677 (17:41159723 G>A), RS1002115487 (17:41160576 C>G), RS1003169253 (17:41162048 A>G), RS1003400157 (17:41162340 G>T), RS1003514837 (17:41162579 T>A), RS1003850575 (17:41160459 G>A,C,T), RS1005156041 (17:41161444 C>T), RS1005628281 (17:41162260 T>A), RS1010551765 (17:41159998 G>A,T), RS1011049544 (17:41162318 G>T), RS1011812809 (17:41161257 A>T)

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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
abrine	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silver	increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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