CYSTM1

Summary

CYSTM1 (cysteine rich transmembrane module containing 1, HGNC:30239) is a protein-coding gene on chromosome 5q31.3, encoding Cysteine-rich transmembrane module-containing protein 1 (Q9H1C7).

Located in extracellular exosome.

Source: NCBI Gene 84418 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_032412

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30239
Approved symbol	CYSTM1
Name	cysteine rich transmembrane module containing 1
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	ORF1-FL49
Ensembl gene	ENSG00000120306
Ensembl biotype	protein_coding
OMIM	621347
Entrez	84418

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000261811, ENST00000504227, ENST00000509589, ENST00000509789, ENST00000644078, ENST00000889043, ENST00000889044, ENST00000889045, ENST00000889046, ENST00000889047, ENST00000921948, ENST00000921949, ENST00000942652

RefSeq mRNA: 1 — MANE Select: NM_032412 NM_032412

CCDS: CCDS4221

Canonical transcript exons

ENST00000261811 — 3 exons

Exon	Start	End
ENSE00001257338	140243305	140243789
ENSE00002075936	140175188	140175285
ENSE00003487504	140194446	140194652

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 85.6911 / max 1202.7708, expressed in 1817 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58888	76.2668	1817
58889	5.9109	1333
58890	2.4092	753
58887	1.1042	800

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pylorus	UBERON:0001166	99.86	gold quality
kidney epithelium	UBERON:0004819	99.77	gold quality
pancreatic ductal cell	CL:0002079	99.73	gold quality
cardia of stomach	UBERON:0001162	99.70	gold quality
renal medulla	UBERON:0000362	99.63	gold quality
jejunal mucosa	UBERON:0000399	99.55	gold quality
ileal mucosa	UBERON:0000331	99.48	gold quality
duodenum	UBERON:0002114	99.42	gold quality
adult mammalian kidney	UBERON:0000082	99.26	gold quality
body of stomach	UBERON:0001161	99.26	gold quality
metanephros cortex	UBERON:0010533	99.26	gold quality
colonic mucosa	UBERON:0000317	99.25	gold quality
tibialis anterior	UBERON:0001385	99.25	gold quality
jejunum	UBERON:0002115	99.22	gold quality
islet of Langerhans	UBERON:0000006	99.17	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.15	gold quality
mucosa of transverse colon	UBERON:0004991	99.08	gold quality
right adrenal gland cortex	UBERON:0035827	99.08	gold quality
stomach	UBERON:0000945	99.07	gold quality
right adrenal gland	UBERON:0001233	99.03	gold quality
epithelial cell of pancreas	CL:0000083	99.02	gold quality
left adrenal gland	UBERON:0001234	99.00	gold quality
gastrocnemius	UBERON:0001388	98.99	gold quality
left adrenal gland cortex	UBERON:0035825	98.99	gold quality
adrenal cortex	UBERON:0001235	98.98	gold quality
quadriceps femoris	UBERON:0001377	98.96	gold quality
biceps brachii	UBERON:0001507	98.95	gold quality
deltoid	UBERON:0001476	98.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.92	gold quality
vastus lateralis	UBERON:0001379	98.91	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	603.12
E-GEOD-98556	yes	447.36
E-MTAB-10485	yes	218.81
E-HCAD-1	yes	77.43
E-MTAB-8410	yes	52.19
E-HCAD-31	yes	34.78
E-HCAD-5	yes	34.55
E-MTAB-5061	yes	27.26
E-GEOD-81547	yes	21.55
E-MTAB-10553	yes	20.99
E-HCAD-11	yes	18.46
E-GEOD-125970	yes	17.25
E-HCAD-10	yes	12.96
E-HCAD-9	yes	11.53
E-GEOD-130148	yes	10.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting CYSTM1, 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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-8086	97.21	64.13	331

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cystm1	ENSMUSG00000046727

Protein

Protein identifiers

Cysteine-rich transmembrane module-containing protein 1 — Q9H1C7 (reviewed: Q9H1C7)

All UniProt accessions (2): Q9H1C7, A0A2R8YEW2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the CYSTM1 family.

RefSeq proteins (1): NP_115788* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028144	CYSTM_dom	Domain
IPR043240	CYSTM1-like	Family

Pfam: PF12734

UniProt features (6 total): compositionally biased region 2, chain 1, transmembrane region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1C7-F1	62.58	0.03

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 167 (showing top): ATF_B, REACTOME_INNATE_IMMUNE_SYSTEM, PAX4_01, GOCC_SECRETORY_GRANULE, GCANCTGNY_MYOD_Q6, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CREBP1_Q2, PATIL_LIVER_CANCER, CREB_Q4, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, INGRAM_SHH_TARGETS_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, ATF3_Q6, CREB_Q2_01, USF_02

GO Biological Process (0):

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

GO Cellular Component (4): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
membrane	1
cell periphery	1
extracellular vesicle	1
secretory granule membrane	1
tertiary granule	1
cellular anatomical structure	1

Protein interactions and networks

STRING

771 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYSTM1	ZNF613	Q6PF04	430
CYSTM1	CKAP4	Q07065	429
CYSTM1	CLEC5A	Q9NY25	427
CYSTM1	PTAFR	P25105	407
CYSTM1	ZBTB18	Q99592	392
CYSTM1	SH2D6	Q7Z4S9	382
CYSTM1	SCARB1	Q8WTV0	374
CYSTM1	CD36	P16671	374
CYSTM1	SCARB2	Q14108	374
CYSTM1	TMEM147	Q9BVK8	373
CYSTM1	IGIP	A6NJ69	357
CYSTM1	KRTCAP2	Q8N6L1	350
CYSTM1	DNAAF8	Q8IYS4	349
CYSTM1	ZNF354B	Q96LW1	348
CYSTM1	NRG2	O14511	342

IntAct

21 interactions, top by confidence:

A	B	Type	Score
SYT16	CYSTM1	psi-mi:“MI:0915”(physical association)	0.560
BAG3	CYSTM1	psi-mi:“MI:0915”(physical association)	0.560
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
MFSD4A	HIP1R	psi-mi:“MI:0914”(association)	0.530
CYSTM1	GLP1R	psi-mi:“MI:0915”(physical association)	0.510
GLP1R	CYSTM1	psi-mi:“MI:0915”(physical association)	0.510
MEP1B	CYSTM1	psi-mi:“MI:0915”(physical association)	0.370
CYSTM1	ARVCF	psi-mi:“MI:0914”(association)	0.350
TM4SF5	PLSCR1	psi-mi:“MI:0914”(association)	0.350
DHRS3	CLPX	psi-mi:“MI:0914”(association)	0.350
CYP3A7	VAPB	psi-mi:“MI:0914”(association)	0.350
CYSTM1	ANKRD13A	psi-mi:“MI:0914”(association)	0.350
SLC35F3	TMEM223	psi-mi:“MI:0914”(association)	0.350
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270
SYT16	CYSTM1	psi-mi:“MI:0915”(physical association)	0.000
BAG3	CYSTM1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): CYSTM1 (Affinity Capture-MS), CYSTM1 (Affinity Capture-MS), CYSTM1 (Affinity Capture-MS), SYT16 (Two-hybrid), BAG3 (Two-hybrid), CYSTM1 (PCA), CYSTM1 (Affinity Capture-MS), ARVCF (Affinity Capture-MS), SRC (Affinity Capture-MS), CYSTM1 (Affinity Capture-MS), CYSTM1 (Affinity Capture-MS), CYSTM1 (Affinity Capture-MS), CYSTM1 (Affinity Capture-MS), CYSTM1 (Affinity Capture-MS), MYADM (Affinity Capture-MS)

ESM2 similar proteins: A0A178WF56, A3A4E0, A5PLE2, B4FF80, B4FUS3, B6TYV8, B6TZ45, D9HP19, D9HP23, D9HP25, D9HP27, I2HB52, O04023, O04133, O22802, O23035, O43125, O60154, O94425, P38216, P40388, P43582, P58196, Q00166, Q12489, Q1PEX8, Q28H62, Q32LK2, Q54YM7, Q55GT2, Q6NN03, Q6Q5X2, Q8K353, Q8L9S1, Q8LCL8, Q8LG30, Q8S8T8, Q8W472, Q94C26, Q94CD4

Diamond homologs: A5PLE2, Q28H62, Q32LK2, Q8K353, Q9H1C7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1303 predictions. Top by Δscore:

Variant	Effect	Δscore
5:140243303:A:AG	acceptor_gain	1.0000
5:140243304:G:GC	acceptor_gain	1.0000
5:140243304:GT:G	acceptor_gain	1.0000
5:140243304:GTGT:G	acceptor_gain	1.0000
5:140246053:TTCTG:T	acceptor_gain	1.0000
5:140246055:CTG:C	acceptor_gain	1.0000
5:140246058:C:CC	acceptor_gain	1.0000
5:140281442:AACTT:A	donor_loss	1.0000
5:140281443:ACTT:A	donor_loss	1.0000
5:140281444:CTTAC:C	donor_loss	1.0000
5:140281445:TTACT:T	donor_loss	1.0000
5:140281446:TA:T	donor_loss	1.0000
5:140281447:A:AC	donor_gain	1.0000
5:140281447:ACT:A	donor_loss	1.0000
5:140281447:ACTT:A	donor_gain	1.0000
5:140281448:C:A	donor_loss	1.0000
5:140281448:C:CA	donor_gain	1.0000
5:140281448:CT:C	donor_gain	1.0000
5:140281448:CTT:C	donor_gain	1.0000
5:140281448:CTTC:C	donor_gain	1.0000
5:140281448:CTTCT:C	donor_gain	1.0000
5:140281450:T:TA	donor_gain	1.0000
5:140281529:TAAAC:T	acceptor_gain	1.0000
5:140281530:AAAC:A	acceptor_gain	1.0000
5:140281531:AAC:A	acceptor_gain	1.0000
5:140281533:CC:C	acceptor_loss	1.0000
5:140281533:CCTA:C	acceptor_gain	1.0000
5:140281534:C:CA	acceptor_loss	1.0000
5:140281534:C:CC	acceptor_gain	1.0000
5:140281536:A:C	acceptor_gain	1.0000

AlphaMissense

611 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:140243374:C:A	A86D	0.997
5:140243382:T:C	C89R	0.997
5:140243364:T:C	C83R	0.996
5:140243385:T:C	C90R	0.996
5:140243379:T:C	C88R	0.995
5:140243388:T:C	C91R	0.995
5:140243362:C:A	A82D	0.993
5:140243383:G:A	C89Y	0.993
5:140243398:A:T	D94V	0.992
5:140243365:G:A	C83Y	0.991
5:140243367:T:A	W84R	0.991
5:140243367:T:C	W84R	0.991
5:140243392:T:C	L92P	0.991
5:140243377:T:A	L87H	0.990
5:140243384:C:G	C89W	0.990
5:140243392:T:A	L92H	0.990
5:140243373:G:C	A86P	0.989
5:140243394:T:A	W93R	0.989
5:140243394:T:C	W93R	0.989
5:140243398:A:C	D94A	0.989
5:140194616:T:A	W51R	0.988
5:140194616:T:C	W51R	0.988
5:140194644:A:T	K60I	0.988
5:140243377:T:C	L87P	0.988
5:140243380:G:A	C88Y	0.988
5:140243397:G:C	D94H	0.988
5:140243386:G:A	C90Y	0.987
5:140194618:G:C	W51C	0.986
5:140194618:G:T	W51C	0.986
5:140243366:C:G	C83W	0.985

dbSNP variants (sampled 300 via entrez): RS1000005370 (5:140220146 T>G), RS1000005432 (5:140178880 G>A,T), RS1000019228 (5:140242786 G>A), RS1000101481 (5:140239108 G>T), RS1000141546 (5:140186285 A>T), RS1000199707 (5:140223688 C>G), RS1000273171 (5:140223194 G>T), RS1000287946 (5:140204114 C>T), RS1000349031 (5:140204356 G>A), RS1000588482 (5:140188227 C>T), RS1000607571 (5:140224961 G>C), RS1000614384 (5:140208505 C>G,T), RS1000623446 (5:140241363 G>A), RS1000745816 (5:140180737 C>A), RS1000777365 (5:140234350 T>C)

Disease associations

OMIM: gene MIM:621347 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005316_640	Intelligence (MTAG)	6.000000e-11
GCST005951_151	Body mass index	6.000000e-07
GCST006946_33	Worry too long after an embarrassing experience	1.000000e-08
GCST010204_165	Low density lipoprotein cholesterol levels	3.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004340	body mass index
EFO:0009589	worry measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Benzo(a)pyrene	affects methylation, increases expression	3
methylmercuric chloride	decreases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
perfluorooctanoic acid	increases expression	1
diallyl trisulfide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
bisphenol S	increases expression, affects cotreatment	1
NSC 689534	affects binding, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Atrazine	increases expression	1
Cadmium	increases palmitoylation, decreases reaction, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2VI	Abcam HEK293T CYSTM1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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