KRTAP12-4

Summary

KRTAP12-4 (keratin associated protein 12-4, HGNC:20532) is a protein-coding gene on chromosome 21q22.3, encoding Keratin-associated protein 12-4 (P60329). 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 386684 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_198698

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20532
Approved symbol	KRTAP12-4
Name	keratin associated protein 12-4
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KRTAP12.4
Ensembl gene	ENSG00000212933
Ensembl biotype	protein_coding
Entrez	386684

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000391618

RefSeq mRNA: 1 — MANE Select: NM_198698 NM_198698

CCDS: CCDS42963

Canonical transcript exons

ENST00000391618 — 1 exons

Exon	Start	End
ENSE00001509396	44654213	44654659

Expression profiles

Bgee: expression breadth tissue_specific, 7 present calls, max score 42.76.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	42.76	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
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
tonsil	UBERON:0002372	31.48	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
blood	UBERON:0000178	30.63	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
leukocyte	CL:0000738	27.43	gold quality
urinary bladder	UBERON:0001255	27.08	gold quality
monocyte	CL:0000576	26.57	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
skin of abdomen	UBERON:0001416	26.04	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
cortex of kidney	UBERON:0001225	25.26	silver quality
muscle of leg	UBERON:0001383	24.92	gold quality
zone of skin	UBERON:0000014	24.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Keratin-associated protein 12-4 — P60329 (reviewed: P60329)

Alternative names: High sulfur keratin-associated protein 12.4, Keratin-associated protein 12.4

All UniProt accessions (1): P60329

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_941971* (*=MANE)

Domains & families (InterPro)

UniProt features (17 total): repeat 15, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60329-F1	44.03	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, CERIBELLI_PROMOTERS_INACTIVE_AND_BOUND_BY_NFY, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, TATA_01, ZAK_PBMC_MRKAD5_HIV_1_GAG_POL_NEF_AGE_20_50YO_CORRELATED_WITH_CD8_T_CELL_RESPONSE_3DY_NEGATIVE, TATAAA_TATA_01

GO Biological Process (0):

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

GO Cellular Component (2): cytosol (GO:0005829), 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
binding	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

82 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP12-4	TMEM167B	Q9NRX6	583
KRTAP12-4	CNTNAP2	Q9UHC6	445
KRTAP12-4	AASS	Q9UDR5	405
KRTAP12-4	KRTAP24-1	Q3LI83	158
KRTAP12-4	KRTAP8-1	Q8IUC2	137
KRTAP12-4	ACTR5	Q9H9F9	102
KRTAP12-4	K7ENP7	K7ENP7	99
KRTAP12-4	INO80C	Q6PI98	99
KRTAP12-4	RUVBL1	P82276	90
KRTAP12-4	RUVBL2	Q9Y230	90
KRTAP12-4	ACTR8	Q9H981	66
KRTAP12-4	KRTAP11-1	Q8IUC1	62
KRTAP12-4	KRTAP10-8	P60410	54
KRTAP12-4	HMGB4	Q8WW32	44
KRTAP12-4	PIH1D2	Q8WWB5	0
KRTAP12-4	TEKT5	Q96M29	0

IntAct

167 interactions, top by confidence:

A	B	Type	Score
HOXA1	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-4	OTX1	psi-mi:“MI:0915”(physical association)	0.720
IQUB	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.720
PIH1D2	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-4	HOXA1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-4	IQUB	psi-mi:“MI:0915”(physical association)	0.720
OTX1	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-4	PIH1D2	psi-mi:“MI:0915”(physical association)	0.720
VENTX	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.670
KRTAP12-4	VENTX	psi-mi:“MI:0915”(physical association)	0.670
KRTAP12-4	KRTAP11-1	psi-mi:“MI:0915”(physical association)	0.600
KRTAP12-4	FBXO34	psi-mi:“MI:0915”(physical association)	0.600
FBXO34	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.600
KRTAP12-4	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.560
HMGB4	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (58): KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), NOTCH2NL (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid), KRTAP12-4 (Two-hybrid)

ESM2 similar proteins: A1A580, A2A591, A2A5X4, A2A5X5, A8MUX0, A8MX34, B2RUR4, O13152, O93499, O93500, P02444, P02445, P02446, P02447, P02449, P02450, P02451, P04458, P07521, P08335, P0DV60, P20307, P20308, P25692, P60329, Q24JX8, Q24JX9, Q3LI81, Q3LI83, Q4KL71, Q5T749, Q5T750, Q5TA77, Q6PEX3, Q6R648, Q6S343, Q7TQM5, Q8IUC1, Q92012, Q98U05

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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	19	39.2×	1e-26
Formation of the cornified envelope	9	29.3×	6e-11

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	10	66.9×	4e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

112 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44654524:AGC:A	donor_gain	0.8600
21:44654411:C:CT	donor_gain	0.7200
21:44654410:C:CT	donor_gain	0.7000
21:44654522:ATAGC:A	donor_gain	0.6700
21:44654245:GCAC:G	acceptor_loss	0.6600
21:44654246:CACC:C	acceptor_loss	0.6600
21:44654247:AC:A	acceptor_loss	0.6600
21:44654248:CC:C	acceptor_loss	0.6600
21:44654249:CT:C	acceptor_loss	0.6600
21:44654250:T:A	acceptor_loss	0.6500
21:44654613:A:C	donor_gain	0.6500
21:44654394:A:AC	donor_gain	0.5900
21:44654395:C:CC	donor_gain	0.5900
21:44654395:CAGG:C	donor_gain	0.5800
21:44654524:AG:A	donor_gain	0.5700
21:44654251:A:C	acceptor_loss	0.5400
21:44654259:CA:C	acceptor_loss	0.5400
21:44654347:C:T	acceptor_gain	0.5400
21:44654406:CAGG:C	donor_gain	0.5300
21:44654409:G:GC	donor_gain	0.5300
21:44654389:AG:A	donor_gain	0.5100
21:44654246:CAC:C	acceptor_gain	0.4900
21:44654525:G:C	donor_gain	0.4900
21:44654396:A:C	donor_gain	0.4800
21:44654249:C:CC	acceptor_gain	0.4600
21:44654390:G:A	donor_gain	0.4600
21:44654260:A:C	acceptor_loss	0.4500
21:44654407:AGGC:A	donor_gain	0.4500
21:44654462:C:CT	donor_gain	0.4500
21:44654526:C:CA	donor_gain	0.4500

AlphaMissense

711 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:44654423:G:C	S64R	0.605
21:44654423:G:T	S64R	0.605
21:44654425:T:G	S64R	0.605
21:44654384:C:A	K77N	0.582
21:44654384:C:G	K77N	0.582

dbSNP variants (sampled 300 via entrez): RS1002764602 (21:44654461 C>A,T), RS1003206995 (21:44654695 C>T), RS1007053549 (21:44654315 G>A,T), RS1011285651 (21:44654384 C>A), RS1012792991 (21:44654730 T>A,G), RS1025600380 (21:44656453 G>C), RS1029335912 (21:44653843 T>C), RS1029830264 (21:44654122 G>T), RS1039419338 (21:44654328 C>A,G,T), RS1040272984 (21:44654613 A>G), RS1042454839 (21:44653776 G>A), RS1055129799 (21:44653804 A>G), RS1055564847 (21:44654093 A>C), RS1057199755 (21:44656654 T>C), RS10580785 (21:44655238 TCTGCA>T,TCTGCACTGCA)

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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Endosulfan	increases expression	1
Pesticides	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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