KRTAP12-3

Summary

KRTAP12-3 (keratin associated protein 12-3, HGNC:20531) is a protein-coding gene on chromosome 21q22.3, encoding Keratin-associated protein 12-3 (P60328). 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….

Enables identical protein binding activity. Predicted to be located in cytosol.

Source: NCBI Gene 386683 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_198697

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20531
Approved symbol	KRTAP12-3
Name	keratin associated protein 12-3
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KRTAP12.3
Ensembl gene	ENSG00000205439
Ensembl biotype	protein_coding
Entrez	386683

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000397907

RefSeq mRNA: 1 — MANE Select: NM_198697 NM_198697

CCDS: CCDS42964

Canonical transcript exons

ENST00000397907 — 1 exons

Exon	Start	End
ENSE00001370311	44657932	44658341

Expression profiles

Bgee: expression breadth broad, 27 present calls, max score 50.20.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	50.20	silver 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
skin of abdomen	UBERON:0001416	33.63	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
blood	UBERON:0000178	32.93	silver quality
zone of skin	UBERON:0000014	32.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
skin of leg	UBERON:0001511	31.68	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.32	silver quality
leukocyte	CL:0000738	28.45	gold quality
liver	UBERON:0002107	28.38	gold quality
duodenum	UBERON:0002114	28.14	gold quality
endocervix	UBERON:0000458	28.08	gold quality
lymph node	UBERON:0000029	27.57	gold quality
monocyte	CL:0000576	27.40	gold quality
islet of Langerhans	UBERON:0000006	27.31	gold quality
tonsil	UBERON:0002372	27.05	gold quality
urinary bladder	UBERON:0001255	26.87	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
uterine cervix	UBERON:0000002	26.40	silver quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.32

Regulation

Is transcription factor: no

Cross-species orthologs

25 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap10-4	ENSMUSG00000069582
mus_musculus	Krtap10-31	ENSMUSG00000071195
mus_musculus	Krtap10-21	ENSMUSG00000094120
mus_musculus	Krtap10-27	ENSMUSG00000094913
mus_musculus	Krtap10-26	ENSMUSG00000095593
mus_musculus	Krtap10-25	ENSMUSG00000095721
mus_musculus	Krtap10-22	ENSMUSG00000095817
mus_musculus	Krtap10-33	ENSMUSG00000095970
mus_musculus	Krtap10-29	ENSMUSG00000096131
mus_musculus	Krtap10-34	ENSMUSG00000096380
mus_musculus	Krtap10-23	ENSMUSG00000096481
mus_musculus	Krtap10-24	ENSMUSG00000111915
mus_musculus	Krtap10-28	ENSMUSG00000112170
mus_musculus	Krtap10-10	ENSMUSG00000112223
mus_musculus	Krtap10-30	ENSMUSG00000112380
mus_musculus	Gm49918	ENSMUSG00000112600
mus_musculus	Krtap10-35	ENSMUSG00000112653
mus_musculus	Krtap10-32	ENSMUSG00000112864
rattus_norvegicus	Krtap10-8l1	ENSRNOG00000001218
rattus_norvegicus	Krtap10-10	ENSRNOG00000032530
rattus_norvegicus	Krtap10-9	ENSRNOG00000043302
rattus_norvegicus	Krtap10-1l1	ENSRNOG00000046538
rattus_norvegicus	Krtap10-1	ENSRNOG00000047532
rattus_norvegicus	LOC120098854	ENSRNOG00000067436
rattus_norvegicus	Krtap10-10l2	ENSRNOG00000069553

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), 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 12-3 — P60328 (reviewed: P60328)

Alternative names: High sulfur keratin-associated protein 12.3, Keratin-associated protein 12.3

All UniProt accessions (1): P60328

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. Restricted to a narrow region of the hair fiber cuticle, lying approximately 20 cell layers above the apex of the dermal papilla of the hair root; not detected in any other tissues.

Similarity. Belongs to the KRTAP type 12 family.

RefSeq proteins (1): NP_941970* (*=MANE)

Domains & families (InterPro)

UniProt features (17 total): repeat 14, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60328-F1	42.53	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: 10 (showing top): chr21q22, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, TATA_01, RTAAACA_FREAC2_01, TATAAA_TATA_01

GO Biological Process (0):

GO Molecular Function (2): identical protein binding (GO:0042802), 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
protein binding	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

176 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP12-3	OR4E2	Q8NGC2	652
KRTAP12-3	OR10Z1	Q8NGY1	643
KRTAP12-3	OR6K6	Q8NGW6	597
KRTAP12-3	OR5C1	Q8NGR4	597
KRTAP12-3	OR51I2	Q9H344	593
KRTAP12-3	KRTAP9-8	Q9BYQ0	583
KRTAP12-3	KRTAP10-8	P60410	583
KRTAP12-3	OR51I1	Q9H343	583
KRTAP12-3	OR1I1	O60431	583
KRTAP12-3	OR10G3	Q8NGC4	582
KRTAP12-3	KRTAP10-7	P60409	580
KRTAP12-3	TMEM235	A6NFC5	542
KRTAP12-3	OR51V1	Q9H2C8	525
KRTAP12-3	OR52K1	Q8NGK4	512
KRTAP12-3	OR4S1	Q8NGB4	507

IntAct

463 interactions, top by confidence:

A	B	Type	Score
ZNF439	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
SLC23A1	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
R3HDM2	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
LCE3E	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
WNT11	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
ZNF408	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
LCE1B	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
ZNF467	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
TCEANC	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
ZNF80	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
SLC13A5	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
C11orf87	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
AGXT	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
LMNTD2	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
ZNF578	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
LCE3A	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
KRTAP12-3	LCE1E	psi-mi:“MI:0915”(physical association)	0.000
NPDC1	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
KRTAP12-3		psi-mi:“MI:0915”(physical association)	0.000
LCE3D	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
CNNM3	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
CARD10	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
KRT20	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
KRTAP12-3	LCE2C	psi-mi:“MI:0915”(physical association)	0.000
PTGDS	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
KRTAP12-3	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.000
DOCK2	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
RSPO2	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
ADAMTSL3	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
ZNF440	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (147): KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP12-3 (Two-hybrid)

ESM2 similar proteins: A5A6P5, A6QP35, A8MTY7, A8MVA2, A8MXZ3, P02438, P02439, P02440, P02441, P02442, P02443, P08131, P0C5Y4, P59990, P59991, P60014, P60328, P60329, P60331, P60368, P60369, P60370, P60371, P60372, P60409, P60410, P60411, P60412, P60413, Q05B44, Q07627, Q3V2C1, Q8IUG1, Q9BQ66, Q9BYP9, Q9BYQ2, Q9BYQ3, Q9BYQ4, Q9BYQ5, Q9BYQ6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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	24	16.5×	5e-21
Formation of the cornified envelope	15	16.3×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	14	29.8×	2e-14

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	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

127 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44658061:G:GG	donor_gain	0.8700
21:44658057:GCCC:G	donor_gain	0.8400
21:44658091:G:GG	donor_gain	0.8400
21:44658087:GCCC:G	donor_gain	0.7800
21:44658051:C:G	donor_gain	0.7500
21:44658044:C:T	donor_gain	0.7400
21:44658151:G:GG	donor_gain	0.6900
21:44658179:C:G	donor_gain	0.6900
21:44658109:GT:G	donor_gain	0.6800
21:44658086:TGCCC:T	donor_gain	0.6600
21:44658087:GCCCG:G	donor_gain	0.6600
21:44658150:C:CG	donor_gain	0.6400
21:44658171:A:G	donor_gain	0.6400
21:44658060:C:CG	donor_gain	0.6000
21:44658139:GT:G	donor_gain	0.5800
21:44658111:G:GG	donor_gain	0.5700
21:44657958:ACC:A	donor_gain	0.5600
21:44658095:GC:G	donor_gain	0.5600
21:44658155:GC:G	donor_gain	0.5600
21:44658090:C:G	donor_gain	0.5500
21:44658156:C:T	donor_gain	0.5500
21:44658066:C:T	donor_gain	0.5400
21:44658096:C:T	donor_gain	0.5400
21:44658065:G:GT	donor_gain	0.5200
21:44657981:T:G	donor_gain	0.5100
21:44658171:A:AG	donor_gain	0.4900
21:44658147:GCCC:G	donor_gain	0.4700
21:44658114:C:A	donor_gain	0.4600
21:44658174:T:G	donor_gain	0.4600
21:44658191:A:AG	acceptor_gain	0.4500

AlphaMissense

622 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000746285 (21:44658598 C>T), RS1005056870 (21:44658521 G>A,T), RS1008314490 (21:44657366 G>A), RS1008699242 (21:44657104 T>A,C,G), RS1013238698 (21:44656678 C>T), RS1014877609 (21:44657801 G>A,C), RS1019629810 (21:44657116 A>G), RS1021632098 (21:44657420 T>A), RS1021920020 (21:44657156 C>T), RS1025600380 (21:44656453 G>C), RS1025716485 (21:44656735 C>G), RS1028658235 (21:44658566 T>C), RS1031839870 (21:44657540 T>C), RS1032371555 (21:44657795 T>A), RS1037325359 (21:44657331 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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Cyclosporine	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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