CYSRT1

Summary

CYSRT1 (cysteine rich tail 1, HGNC:30529) is a protein-coding gene on chromosome 9q34.3, encoding Cysteine-rich tail protein 1 (A8MQ03). Component of the stratum corneum that may contribute to epidermal antimicrobial host defenses.

Enables identical protein binding activity. Involved in biological process involved in interaction with symbiont and establishment of skin barrier. Located in cornified envelope.

Source: NCBI Gene 375791 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_199001

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30529
Approved symbol	CYSRT1
Name	cysteine rich tail 1
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC59937
Ensembl gene	ENSG00000197191
Ensembl biotype	protein_coding
OMIM	621357
Entrez	375791

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000650725

RefSeq mRNA: 1 — MANE Select: NM_199001 NM_199001

CCDS: CCDS48064

Canonical transcript exons

ENST00000650725 — 2 exons

Exon	Start	End
ENSE00003994069	137225174	137225233
ENSE00003994082	137225614	137226315

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 99.52.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3967 / max 347.3082, expressed in 406 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99676	2.2696	387
99675	0.0923	45
99674	0.0194	5
99673	0.0154	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.52	gold quality
buccal mucosa cell	CL:0002336	98.80	gold quality
esophagus mucosa	UBERON:0002469	98.09	gold quality
pharyngeal mucosa	UBERON:0000355	97.14	gold quality
esophagus squamous epithelium	UBERON:0006920	97.11	gold quality
oral cavity	UBERON:0000167	96.77	gold quality
gingiva	UBERON:0001828	94.68	gold quality
gingival epithelium	UBERON:0001949	94.12	gold quality
skin of leg	UBERON:0001511	92.11	gold quality
skin of abdomen	UBERON:0001416	90.32	gold quality
zone of skin	UBERON:0000014	89.45	gold quality
amniotic fluid	UBERON:0000173	89.00	gold quality
right uterine tube	UBERON:0001302	85.72	gold quality
penis	UBERON:0000989	85.55	gold quality
vagina	UBERON:0000996	85.17	gold quality
adenohypophysis	UBERON:0002196	82.95	gold quality
esophagus	UBERON:0001043	82.80	gold quality
pituitary gland	UBERON:0000007	81.26	gold quality
upper leg skin	UBERON:0004262	80.65	gold quality
mammalian vulva	UBERON:0000997	80.15	gold quality
body of tongue	UBERON:0011876	79.56	gold quality
mouth mucosa	UBERON:0003729	78.82	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.33	gold quality
minor salivary gland	UBERON:0001830	76.36	gold quality
skin of hip	UBERON:0001554	74.03	gold quality
tonsil	UBERON:0002372	73.17	gold quality
saliva-secreting gland	UBERON:0001044	73.11	gold quality
tendon of biceps brachii	UBERON:0008188	72.62	gold quality
metanephros cortex	UBERON:0010533	72.52	gold quality
tongue	UBERON:0001723	72.21	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	3611.58
E-ANND-3	yes	6.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting CYSRT1, 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-661	99.09	65.94	2062
HSA-MIR-3620-3P	97.78	64.88	772
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-4449	88.89	64.59	48

Literature-anchored findings (GeneRIF, showing 1)

• CYSRT1: An Antimicrobial Epidermal Protein that Can Interact with Late Cornified Envelope Proteins. (PMID:36804407)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cysrt1	ENSMUSG00000036731
rattus_norvegicus	Cysrt1	ENSRNOG00000010600

Protein

Protein identifiers

Cysteine-rich tail protein 1 — A8MQ03 (reviewed: A8MQ03)

All UniProt accessions (1): A8MQ03

UniProt curated annotations — full annotation on UniProt →

Function. Component of the stratum corneum that may contribute to epidermal antimicrobial host defenses.

Subunit / interactions. Interacts with LCE1B; the interaction is direct. Interacts with LCE2C; the interaction is direct. Interacts with LCE3A; the interaction is direct. Interacts with LCE3C; the interaction is direct. Interacts with LCE4A; the interaction is direct. Interacts with LCE5A; the interaction is direct. Interacts with LCE1C. Interacts with LCE1D. Interacts with LCE1E. Interacts with LCE2A. Interacts with LCE3D. Interacts with LCE3E. Interacts with LCE1A.

Subcellular location. Cornified envelope.

Tissue specificity. Expressed in the stratum granulosum, in skin and oral epithelia (at protein level).

Similarity. Belongs to the CYSRT1 family.

RefSeq proteins (1): NP_945352* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018904	UPF0574	Family

Pfam: PF10631

UniProt features (4 total): chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MQ03-F1	56.71	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MARTINEZ_RB1_TARGETS_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_SYMBIONT, GOBP_SKIN_DEVELOPMENT, MARTINEZ_RB1_AND_TP53_TARGETS_UP, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, GOCC_CORNIFIED_ENVELOPE, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MIKKELSEN_IPS_LCP_WITH_H3K4ME3, MIKKELSEN_ES_LCP_WITH_H3K4ME3, MIKKELSEN_NPC_WITH_LCP_H3K27ME3

GO Biological Process (2): biological process involved in interaction with symbiont (GO:0051702), establishment of skin barrier (GO:0061436)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (2): cornified envelope (GO:0001533), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
biological process involved in symbiotic interaction	1
skin epidermis development	1
protein binding	1
binding	1
plasma membrane	1
extracellular vesicle	1

Protein interactions and networks

STRING

220 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYSRT1	SMIM5	Q71RC9	593
CYSRT1	ZNF587	Q96SQ5	589
CYSRT1	TRAF1	Q13077	464
CYSRT1	KRT78	Q8N1N4	449
CYSRT1	TMEM50A	O95807	447
CYSRT1	GGT6	Q6P531	438
CYSRT1	SOWAHB	A6NEL2	398
CYSRT1	KRTAP13-1	Q8IUC0	377
CYSRT1	SH3BP5L	Q7L8J4	369
CYSRT1	WRAP73	Q9P2S5	349
CYSRT1	WSB2	Q9NYS7	348
CYSRT1	LRRC26	Q2I0M4	336
CYSRT1	ASPRV1	Q53RT3	324
CYSRT1	LSM12	Q3MHD2	310
CYSRT1	CNFN	Q9BYD5	305

IntAct

1671 interactions, top by confidence:

A	B	Type	Score
CYSRT1	KRTAP1-3	psi-mi:“MI:0915”(physical association)	0.740
CYSRT1	LCE1D	psi-mi:“MI:0915”(physical association)	0.700
LCE1D	CYSRT1	psi-mi:“MI:0915”(physical association)	0.700
DVL3	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
PTGDS	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
TCF7L2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
GLB1L2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
DOCK2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
PCSK5	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
KRTAP9-2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
KRTAP4-12	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
MGC50722	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
CYSRT1		psi-mi:“MI:0915”(physical association)	0.000
PGAP2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
KRTAP5-11	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
TSPAN4	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
PVR	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
BAG6	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
TNIP3	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
LCE2B	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
TBX2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
HSBP1	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
CYSRT1	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.000
SPMIP2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
GATA3	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
TFAP2D	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
SLC43A2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
KRTAP5-4	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (514): KRTAP1-3 (Two-hybrid), LCE1D (Two-hybrid), CYSRT1 (Affinity Capture-MS), CYSRT1 (Affinity Capture-MS), CYSRT1 (Proximity Label-MS), CYSRT1 (Two-hybrid), CYSRT1 (Two-hybrid), CYSRT1 (Two-hybrid), CYSRT1 (Two-hybrid), CYSRT1 (Two-hybrid), CYSRT1 (Two-hybrid), CYSRT1 (Two-hybrid), CYSRT1 (Two-hybrid), CYSRT1 (Two-hybrid), CYSRT1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GVZ6, A0JNN6, A2A9F4, A6NDZ8, A6NE82, A6NJ08, A6NJB7, A7MB40, A8MQ03, D2HS03, O43151, O93343, O94850, O95886, P01099, P97838, Q00587, Q0VBZ8, Q2KJ10, Q2M2S6, Q3KP66, Q58CU6, Q5NCP0, Q5RBE4, Q64322, Q68DV7, Q6AY88, Q6PFD5, Q7TN12, Q80V38, Q86YN6, Q86YV5, Q8BFY7, Q8BG87, Q8NAX2, Q8NC06, Q8NHZ7, Q8TEF2, Q91XA5, Q96EL1

Diamond homologs: A0JNN6, A8MQ03, Q9D1E4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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	21	10.8×	9e-14
Formation of the cornified envelope	8	6.5×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	7	10.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

53 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137225605:C:G	acceptor_gain	1.0000
9:137225599:T:A	acceptor_gain	0.9900
9:137225604:A:AG	acceptor_gain	0.9900
9:137225609:T:TA	acceptor_gain	0.9900
9:137225609:TGCA:T	acceptor_loss	0.9900
9:137225610:GCAG:G	acceptor_loss	0.9900
9:137225611:CAGGC:C	acceptor_loss	0.9900
9:137225612:A:AG	acceptor_gain	0.9900
9:137225612:AG:A	acceptor_gain	0.9900
9:137225612:AGGCT:A	acceptor_gain	0.9900
9:137225613:G:GT	acceptor_gain	0.9900
9:137225613:GG:G	acceptor_gain	0.9900
9:137225613:GGC:G	acceptor_gain	0.9900
9:137225613:GGCT:G	acceptor_gain	0.9900
9:137225613:GGCTG:G	acceptor_gain	0.9900
9:137225231:CAGG:C	donor_loss	0.9500
9:137225232:AGG:A	donor_loss	0.9500
9:137225233:GGTAA:G	donor_loss	0.9500
9:137225235:T:A	donor_loss	0.9500
9:137225234:G:GG	donor_gain	0.8900
9:137225231:CAG:C	donor_gain	0.8600
9:137225232:AG:A	donor_gain	0.7800
9:137225233:GG:G	donor_gain	0.7800
9:137225230:ACAG:A	donor_gain	0.7700
9:137225516:C:T	donor_gain	0.7400
9:137225229:CACAG:C	donor_gain	0.7200
9:137225613:G:T	acceptor_gain	0.6700
9:137225612:A:T	acceptor_gain	0.6500
9:137225611:CAGG:C	acceptor_gain	0.6400
9:137225234:GT:G	donor_gain	0.6100

AlphaMissense

941 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137225671:T:C	I17T	0.967
9:137225671:T:G	I17S	0.926
9:137226008:C:G	C129W	0.918
9:137226006:T:C	C129R	0.916
9:137226020:C:G	C133W	0.904
9:137225975:C:G	C118W	0.901
9:137226024:T:C	C135R	0.897
9:137226019:G:A	C133Y	0.896
9:137226018:T:C	C133R	0.891
9:137225671:T:A	I17N	0.890
9:137225979:T:C	C120R	0.889
9:137225967:C:G	H116D	0.887
9:137226015:T:C	F132L	0.886
9:137226017:C:A	F132L	0.886
9:137226017:C:G	F132L	0.886
9:137226024:T:A	C135S	0.886
9:137226025:G:C	C135S	0.886
9:137226018:T:A	C133S	0.884
9:137226019:G:C	C133S	0.884
9:137225651:C:A	N10K	0.882
9:137225651:C:G	N10K	0.882
9:137225981:C:G	C120W	0.882
9:137226006:T:A	C129S	0.876
9:137226007:G:C	C129S	0.876
9:137225648:G:C	K9N	0.871
9:137225648:G:T	K9N	0.871
9:137226007:G:A	C129Y	0.871
9:137225667:A:C	S16R	0.869
9:137225669:C:A	S16R	0.869
9:137225669:C:G	S16R	0.869

dbSNP variants (sampled 300 via entrez): RS1000364277 (9:137224936 T>A), RS1000707195 (9:137223492 C>G,T), RS1000770746 (9:137223767 G>A,C), RS1000987831 (9:137223515 C>G), RS1001645598 (9:137226022 G>A,T), RS1002217239 (9:137224173 C>A,T), RS1003213445 (9:137225251 G>A,C), RS1003267581 (9:137225071 G>A,C,T), RS1003868546 (9:137225324 T>C,G), RS1005514035 (9:137224166 G>A,C), RS1005573864 (9:137226701 T>C), RS1006517181 (9:137224703 A>G), RS1007230098 (9:137223228 G>A), RS1008146190 (9:137223523 G>A), RS1008197032 (9:137223660 T>A,C,G)

Disease associations

OMIM: gene MIM:621357 | 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

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression, affects cotreatment	4
Cadmium Chloride	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Estradiol	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
sodium arsenate	increases abundance, decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	increases abundance, increases expression	1
ferrous chloride	decreases expression	1
hydroquinone	increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
chromium hexavalent ion	increases expression, increases abundance	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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