KRT38

Summary

KRT38 (keratin 38, HGNC:6456) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cuticular Ha8 (O76015).

The protein encoded by this gene is a member of the keratin gene family. As a type I hair keratin, it is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription.

Source: NCBI Gene 8687 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_006771

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6456
Approved symbol	KRT38
Name	keratin 38
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171360
Ensembl biotype	protein_coding
OMIM	604542
Entrez	8687

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000246646

RefSeq mRNA: 1 — MANE Select: NM_006771 NM_006771

CCDS: CCDS11392

Canonical transcript exons

ENST00000246646 — 7 exons

Exon	Start	End
ENSE00001250051	41436154	41437541
ENSE00002336607	41439203	41439359
ENSE00002369656	41440430	41440983
ENSE00002379372	41438093	41438313
ENSE00002390160	41440161	41440243
ENSE00002398616	41438491	41438616
ENSE00002418883	41438697	41438858

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 73.26.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	73.26	silver quality
ileal mucosa	UBERON:0000331	64.98	silver quality
hair follicle	UBERON:0002073	60.03	silver quality
upper leg skin	UBERON:0004262	59.61	silver quality
deltoid	UBERON:0001476	57.71	gold quality
skin of hip	UBERON:0001554	57.29	silver quality
decidua	UBERON:0002450	56.55	gold quality
pancreatic ductal cell	CL:0002079	55.65	silver quality
epithelial cell of pancreas	CL:0000083	50.44	gold quality
quadriceps femoris	UBERON:0001377	50.06	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
nasal cavity epithelium	UBERON:0005384	47.70	gold quality
thymus	UBERON:0002370	47.42	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting KRT38, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-3925-5P	99.21	67.90	1466

Cross-species orthologs

0 orthologs

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Keratin, type I cuticular Ha8 — O76015 (reviewed: O76015)

Alternative names: Hair keratin, type I Ha8, Keratin-38

All UniProt accessions (1): O76015

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic).

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_006762* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002957	Keratin_I	Family
IPR018039	IF_conserved	Conserved_site
IPR039008	IF_rod_dom	Domain

Pfam: PF00038

UniProt features (12 total): region of interest 7, chain 1, domain 1, sequence variant 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76015-F1	75.92	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 353 (stutter)

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-6809371	Formation of the cornified envelope
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 44 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, GOBP_TISSUE_MORPHOGENESIS, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, CAMPS_COLON_CANCER_COPY_NUMBER_UP, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, MARTENS_TRETINOIN_RESPONSE_UP, GOBP_SUPRAMOLECULAR_FIBER_ORGANIZATION, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER

GO Biological Process (3): morphogenesis of an epithelium (GO:0002009), epithelial cell differentiation (GO:0030855), intermediate filament organization (GO:0045109)

GO Molecular Function (3): structural molecule activity (GO:0005198), structural constituent of skin epidermis (GO:0030280), protein binding (GO:0005515)

GO Cellular Component (5): cytosol (GO:0005829), cytoskeleton (GO:0005856), keratin filament (GO:0045095), extracellular exosome (GO:0070062), intermediate filament (GO:0005882)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Biology	1
Keratinization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
epithelium development	2
tissue morphogenesis	1
cell differentiation	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
molecular_function	1
structural molecule activity	1
binding	1
cytoplasm	1
cellular anatomical structure	1
intracellular membraneless organelle	1
intermediate filament	1
extracellular vesicle	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT38	KRTAP11-1	Q8IUC1	521
KRT38	KRTAP3-1	Q9BYR8	520
KRT38	KRTAP15-1	Q3LI76	490
KRT38	KRTAP10-9	P60411	481
KRT38	KRTAP10-3	P60369	449
KRT38	KRTAP10-4	P60372	448
KRT38	KRTAP13-1	Q8IUC0	446
KRT38	KRTAP10-11	P60412	437
KRT38	KRTAP10-5	P60370	402
KRT38	ZNF714	Q96N38	398
KRT38	KRTAP10-7	P60409	396
KRT38	PABIR3	Q6P4D5	390
KRT38	KRTDAP	P60985	383
KRT38	KRTAP10-8	P60410	382
KRT38	KRTAP7-1	Q8IUC3	381

IntAct

350 interactions, top by confidence:

A	B	Type	Score
KRT6A	KRT38	psi-mi:“MI:0915”(physical association)	0.890
KRT38	KRT6A	psi-mi:“MI:0915”(physical association)	0.890
KRT38	KRT2	psi-mi:“MI:0915”(physical association)	0.840
KRT2	KRT38	psi-mi:“MI:0915”(physical association)	0.840
KRT38	KRT4	psi-mi:“MI:0915”(physical association)	0.830
TXLNB	KRT38	psi-mi:“MI:0915”(physical association)	0.830
KRT38	SCNM1	psi-mi:“MI:0915”(physical association)	0.830
KRT4	KRT38	psi-mi:“MI:0915”(physical association)	0.830
SCNM1	KRT38	psi-mi:“MI:0915”(physical association)	0.830

BioGRID (224): KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid), KRT38 (Two-hybrid)

ESM2 similar proteins: A0JND2, A3KN27, A6BLY7, A6H712, A6QNX5, A6QQJ3, A7YWK3, D3ZER2, E1AB55, O76014, O76015, P08552, P15331, P21807, P35617, P41219, P46660, P48670, Q0VBK2, Q13515, Q148H5, Q148H6, Q148H8, Q14CN4, Q28177, Q3SY84, Q3TRJ4, Q6A162, Q6IFW3, Q6IFW8, Q6IFX0, Q6IFX4, Q6IFZ9, Q6IG04, Q6IME9, Q6IMF1, Q6KB66, Q6NVD9, Q6NXH9, Q7RTS7

Diamond homologs: A1L317, A1L595, A5A6M0, A5A6M5, A5A6N2, A5A6P3, A6BLY7, A6H712, A6QQQ9, A7YWM2, B0LKP1, B1AQ75, O18740, O57611, O76009, O76011, O76013, O76015, O77727, O93256, P02533, P02534, P02535, P02537, P05781, P06394, P08727, P08728, P08730, P08777, P08778, P08779, P13645, P13646, P19001, P19012, P25030, P25690, P35527, P35900

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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
Formation of the cornified envelope	11	30.2×	7e-12
Keratinization	11	19.1×	5e-10

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	10	63.4×	5e-14
keratinization	10	61.6×	5e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

515 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41438086:CACGT:C	donor_loss	1.0000
17:41438087:ACGT:A	donor_loss	1.0000
17:41438088:CGTAC:C	donor_loss	1.0000
17:41438089:GTA:G	donor_loss	1.0000
17:41438090:T:TG	donor_loss	1.0000
17:41438091:A:AC	donor_gain	1.0000
17:41438091:A:AT	donor_loss	1.0000
17:41438092:C:CG	donor_gain	1.0000
17:41438092:CTTG:C	donor_gain	1.0000
17:41438095:G:A	donor_gain	1.0000
17:41438099:T:TA	donor_gain	1.0000
17:41438108:T:A	donor_gain	1.0000
17:41438309:TCCTT:T	acceptor_gain	1.0000
17:41438310:CCTTC:C	acceptor_gain	1.0000
17:41438311:CTT:C	acceptor_gain	1.0000
17:41438312:TT:T	acceptor_gain	1.0000
17:41438313:TC:T	acceptor_loss	1.0000
17:41438314:C:CC	acceptor_gain	1.0000
17:41438315:T:C	acceptor_loss	1.0000
17:41438316:G:C	acceptor_gain	1.0000
17:41438316:G:GC	acceptor_gain	1.0000
17:41438319:G:C	acceptor_gain	1.0000
17:41438319:G:GC	acceptor_gain	1.0000
17:41438326:A:AC	acceptor_gain	1.0000
17:41438326:A:C	acceptor_gain	1.0000
17:41438487:GTAC:G	donor_loss	1.0000
17:41438488:TA:T	donor_loss	1.0000
17:41438489:A:AC	donor_gain	1.0000
17:41438489:AC:A	donor_gain	1.0000
17:41438489:ACCAA:A	donor_loss	1.0000

AlphaMissense

2988 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41440581:C:G	R114P	0.990
17:41438195:A:G	L380P	0.982
17:41438189:C:G	R382P	0.980
17:41438114:A:G	L407P	0.979
17:41438144:A:G	L397P	0.979
17:41440576:C:G	A116P	0.979
17:41438120:C:G	R405P	0.978
17:41438204:C:G	R377P	0.977
17:41438216:A:G	L373P	0.977
17:41438186:T:G	Q383P	0.975
17:41440578:A:G	L115P	0.975
17:41438165:A:G	L390P	0.972
17:41438124:A:G	Y404H	0.970
17:41440548:A:G	L125P	0.967
17:41440566:A:G	L119P	0.967
17:41440578:A:T	L115Q	0.965
17:41438132:A:C	I401S	0.963
17:41440554:C:G	R123P	0.962
17:41438152:C:A	K394N	0.961
17:41438152:C:G	K394N	0.961
17:41438124:A:C	Y404D	0.958
17:41440582:G:T	R114S	0.958
17:41440587:T:A	N112I	0.958
17:41438135:T:A	E400V	0.956
17:41438202:C:G	A378P	0.955
17:41440590:A:G	L111P	0.955
17:41438162:A:G	L391P	0.949
17:41440192:C:G	A182P	0.949
17:41438147:C:G	R396P	0.943
17:41438175:A:C	Y387D	0.942

dbSNP variants (sampled 300 via entrez): RS1000143898 (17:41437632 A>G), RS1001820607 (17:41441598 A>C,G), RS1002011815 (17:41440180 C>T), RS1002068367 (17:41441304 C>T), RS1002126661 (17:41442708 A>G), RS1002539244 (17:41437356 A>G), RS1004180826 (17:41442680 G>T), RS1004594981 (17:41436691 A>C,G), RS1005295927 (17:41435789 T>C), RS1006715257 (17:41437983 G>T), RS1006935776 (17:41439139 G>A,T), RS1008314925 (17:41441729 G>A), RS1008341668 (17:41442049 C>A,T), RS1008370915 (17:41436372 A>G), RS1008403481 (17:41436699 T>C)

Disease associations

OMIM: gene MIM:604542 | 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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Folic Acid	decreases expression	1
Valproic Acid	increases methylation	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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