KRTAP21-3

Summary

KRTAP21-3 (keratin associated protein 21-3, HGNC:34216) is a protein-coding gene on chromosome 21q22.11, encoding Keratin-associated protein 21-3 (Q3LHN1). 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 100288323 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_001164435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34216
Approved symbol	KRTAP21-3
Name	keratin associated protein 21-3
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000231068
Ensembl biotype	protein_coding
Entrez	100288323

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000444335

RefSeq mRNA: 1 — MANE Select: NM_001164435 NM_001164435

CCDS: CCDS54481

Canonical transcript exons

ENST00000444335 — 1 exons

Exon	Start	End
ENSE00001667917	30718525	30718777

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 93.15.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.48	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
sural nerve	UBERON:0015488	30.93	gold 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
monocyte	CL:0000576	28.07	gold quality
liver	UBERON:0002107	28.04	gold quality
leukocyte	CL:0000738	28.03	gold quality
lymph node	UBERON:0000029	27.57	gold quality
islet of Langerhans	UBERON:0000006	27.27	gold quality
tonsil	UBERON:0002372	27.05	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
blood	UBERON:0000178	25.83	silver quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
muscle of leg	UBERON:0001383	24.74	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
pancreas	UBERON:0001264	24.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Keratin-associated protein 21-3 — Q3LHN1 (reviewed: Q3LHN1)

All UniProt accessions (1): Q3LHN1

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.

RefSeq proteins (1): NP_001157907* (*=MANE)

Domains & families (InterPro)

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3LHN1-F1	42.39	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: 6 (showing top): chr21q22, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER

GO Biological Process (0):

GO Molecular Function (0):

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

Protein interactions and networks

STRING

20 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP21-3	KRTAP21-2	Q3LI59	785
KRTAP21-3	KRTAP21-1	Q3LI58	770
KRTAP21-3	KRTAP7-1	Q8IUC3	670
KRTAP21-3	KRTAP8-1	Q8IUC2	663
KRTAP21-3	USP25	Q9UHP3	430
KRTAP21-3	USP15	Q9Y4E8	182
KRTAP21-3	KRTAP22-1	Q3MIV0	0
KRTAP21-3	LCE3B	Q5TA77	0
KRTAP21-3	KRTAP23-1	A1A580	0
KRTAP21-3	KRTAP22-2	Q3LI68	0

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A183, A1A580, G2TRR9, O09133, O54835, P02446, P02447, P02449, P04869, P07521, P08335, P0DM49, P0DM52, P13411, P13524, P13525, P20308, P23252, P30927, P30928, P33483, P60167, Q03556, Q09360, Q197E2, Q24JX8, Q3LHN1, Q54GV2, Q54LF2, Q54SP7, Q54UL3, Q55AF0, Q55BU0, Q55FC6, Q55FC7, Q5UP52, Q5UQ01, Q5UQP5, Q65675, Q68FV4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

100 predictions. Top by Δscore:

Variant	Effect	Δscore
21:30718655:A:C	donor_gain	0.6900
21:30718699:CACA:C	donor_gain	0.6900
21:30718700:ACAA:A	donor_gain	0.6900
21:30718701:CAAC:C	donor_gain	0.6900
21:30718760:A:AC	donor_gain	0.6700
21:30718701:CAA:C	donor_gain	0.6500
21:30718659:CCG:C	donor_gain	0.6100
21:30718702:A:AT	donor_gain	0.6100
21:30718739:A:AC	donor_gain	0.6100
21:30718740:C:CC	donor_gain	0.6100
21:30718756:A:AC	donor_gain	0.6100
21:30718757:C:CC	donor_gain	0.6100
21:30718698:C:T	donor_gain	0.5900
21:30718657:A:T	donor_gain	0.5800
21:30718697:CCCA:C	donor_gain	0.5800
21:30718698:CCAC:C	donor_gain	0.5800
21:30718761:G:C	donor_gain	0.5800
21:30718660:C:CT	donor_gain	0.5700
21:30718738:CA:C	donor_gain	0.5700
21:30718758:A:C	donor_gain	0.5700
21:30718688:ACAGC:A	donor_gain	0.5300
21:30718689:CAGCC:C	donor_gain	0.5300
21:30718690:AGCCA:A	donor_gain	0.5300
21:30718648:A:AT	donor_gain	0.4900
21:30718653:TAATA:T	donor_gain	0.4900
21:30718654:AATAA:A	donor_gain	0.4900
21:30718753:A:AC	donor_gain	0.4800
21:30718760:AGTGT:A	donor_gain	0.4800
21:30718565:C:CC	acceptor_gain	0.4600
21:30718702:A:C	donor_gain	0.4600

AlphaMissense

387 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:30718709:G:C	C17W	0.812
21:30718688:A:C	C24W	0.807
21:30718751:G:C	F3L	0.798
21:30718751:G:T	F3L	0.798
21:30718753:A:G	F3L	0.798
21:30718690:A:G	C24R	0.793
21:30718670:A:C	C30W	0.779
21:30718711:A:G	C17R	0.767
21:30718702:A:G	C20R	0.755
21:30718724:A:C	C12W	0.752
21:30718672:A:G	C30R	0.744
21:30718700:A:C	C20W	0.742
21:30718666:A:G	C32R	0.734
21:30718718:A:C	F14L	0.733
21:30718718:A:T	F14L	0.733
21:30718720:A:G	F14L	0.733
21:30718671:C:G	C30S	0.727
21:30718672:A:T	C30S	0.727
21:30718733:A:C	C9W	0.721
21:30718689:C:G	C24S	0.716
21:30718690:A:T	C24S	0.716
21:30718607:A:C	F51L	0.714
21:30718607:A:T	F51L	0.714
21:30718609:A:G	F51L	0.714
21:30718726:A:G	C12R	0.713
21:30718735:A:G	C9R	0.695
21:30718664:A:C	C32W	0.688
21:30718665:C:G	C32S	0.680
21:30718666:A:T	C32S	0.680
21:30718701:C:G	C20S	0.673

dbSNP variants (sampled 300 via entrez): RS1000487067 (21:30720093 T>C), RS1001400458 (21:30719650 A>G), RS1005354466 (21:30718536 T>C), RS1005489866 (21:30718040 T>A), RS1005723664 (21:30718914 G>C,T), RS1011864817 (21:30719351 C>A,G), RS1016493648 (21:30720055 C>A), RS1016719144 (21:30718922 C>A), RS1016831371 (21:30718069 T>C), RS1016862058 (21:30718546 A>C), RS1018365686 (21:30720237 T>C), RS1018393419 (21:30720471 T>C), RS1021552910 (21:30718044 T>C), RS1023226339 (21:30719791 T>C), RS1026758097 (21:30720511 T>C,G)

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

1 associations (top):

Study	Trait	p-value
GCST009310_19	Sensorimotor dexterity	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008354	cognitive function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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