CCSER1

Summary

CCSER1 (coiled-coil serine rich protein 1, HGNC:29349) is a protein-coding gene on chromosome 4q22.1, encoding Serine-rich coiled-coil domain-containing protein 1 (Q9C0I3).

Implicated in cocaine dependence.

Source: NCBI Gene 401145 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 172 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001145065

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29349
Approved symbol	CCSER1
Name	coiled-coil serine rich protein 1
Location	4q22.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1680
Ensembl gene	ENSG00000184305
Ensembl biotype	protein_coding
OMIM	618934
Entrez	401145

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 5 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000432775, ENST00000502478, ENST00000503421, ENST00000504150, ENST00000505073, ENST00000508086, ENST00000508550, ENST00000509109, ENST00000509176, ENST00000510519, ENST00000513522, ENST00000514352, ENST00000515693, ENST00000649522

RefSeq mRNA: 3 — MANE Select: NM_001145065 NM_001145065, NM_001377987, NM_207491

CCDS: CCDS47099, CCDS47100

Canonical transcript exons

ENST00000509176 — 11 exons

Exon	Start	End
ENSE00001292028	90308244	90309608
ENSE00001629584	90628025	90628232
ENSE00001709158	90468234	90468354
ENSE00002030953	90127394	90127831
ENSE00002031139	91598572	91605295
ENSE00002192057	90312863	90313047
ENSE00003477601	91085950	91085994
ENSE00003526049	90400036	90400129
ENSE00003601966	90923370	90923447
ENSE00003636512	90723914	90723991
ENSE00003682656	90815762	90815845

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 86.89.

FANTOM5 (CAGE): breadth broad, TPM avg 6.5320 / max 679.5099, expressed in 756 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48868	2.6038	576
48865	1.9127	449
48869	1.5475	446
48867	0.2704	130
48866	0.1935	105
48872	0.0041	3

Top tissues by expression

244 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	86.89	gold quality
right testis	UBERON:0004534	85.91	gold quality
left testis	UBERON:0004533	85.82	gold quality
testis	UBERON:0000473	83.05	gold quality
bone marrow cell	CL:0002092	82.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.88	gold quality
colonic epithelium	UBERON:0000397	78.21	gold quality
cortical plate	UBERON:0005343	75.93	gold quality
sural nerve	UBERON:0015488	75.12	gold quality
islet of Langerhans	UBERON:0000006	74.82	gold quality
calcaneal tendon	UBERON:0003701	74.65	gold quality
ganglionic eminence	UBERON:0004023	74.50	gold quality
rectum	UBERON:0001052	73.95	gold quality
right atrium auricular region	UBERON:0006631	71.76	gold quality
cardiac atrium	UBERON:0002081	70.96	gold quality
apex of heart	UBERON:0002098	70.96	gold quality
heart left ventricle	UBERON:0002084	70.66	gold quality
smooth muscle tissue	UBERON:0001135	70.45	gold quality
right uterine tube	UBERON:0001302	70.33	gold quality
adult mammalian kidney	UBERON:0000082	70.08	gold quality
minor salivary gland	UBERON:0001830	70.07	gold quality
cardiac ventricle	UBERON:0002082	69.64	gold quality
tonsil	UBERON:0002372	69.26	gold quality
buccal mucosa cell	CL:0002336	69.18	gold quality
lymph node	UBERON:0000029	69.14	gold quality
pancreas	UBERON:0001264	68.86	gold quality
heart	UBERON:0000948	68.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.23	gold quality
gall bladder	UBERON:0002110	68.06	gold quality
saliva-secreting gland	UBERON:0001044	67.82	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	8043.45
E-GEOD-131882	yes	7600.15
E-HCAD-35	yes	93.64
E-HCAD-25	yes	79.69
E-HCAD-5	yes	12.53
E-MTAB-6678	yes	7.08
E-CURD-114	yes	6.63
E-ANND-3	yes	4.92
E-CURD-135	no	453.33
E-MTAB-8410	no	3.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

200 targeting CCSER1, 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-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593

Literature-anchored findings (GeneRIF, showing 3)

• Two SNPs located in genes coding for as yet uncharacterized proteins expressed in the cerebellum, XKR4 in 8q12.1, and FAM190A in 4q22.1 suggest association with association with attention deficit hyperactivity disorder. [FAM190A] (PMID:20607790)
• FAM190A is a regulator or structural component required for normal mitosis and that both the rare truncating mutations and common in-frame deletion alteration of FAM190A may contribute to the chromosomal instability of cancer. (PMID:23665203)
• Deletion of a pseudogene within a fragile site triggers the oncogenic expression of the mitotic CCSER1 gene. (PMID:34187875)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccser1	ENSDARG00000075919
mus_musculus	Ccser1	ENSMUSG00000039578
rattus_norvegicus	Ccser1	ENSRNOG00000029321

Paralogs (1): CCSER2 (ENSG00000107771)

Protein

Protein identifiers

Serine-rich coiled-coil domain-containing protein 1 — Q9C0I3 (reviewed: Q9C0I3)

Alternative names: Coiled-coil serine-rich protein 1

All UniProt accessions (7): A0A3B3ITL2, D6RAM2, D6RAM6, E7EUW0, Q9C0I3, H0YA74, H0YAI2

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the CCSER family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C0I3-1	1	yes
Q9C0I3-2	2

RefSeq proteins (3): NP_001138537, NP_001364916, NP_997374 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029627	CCSER	Family

UniProt features (9 total): region of interest 2, compositionally biased region 2, splice variant 2, chain 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0I3-F1	47.56	0.05

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 133 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_PROTEIN_ACTIVATION_CASCADE, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, DAWSON_METHYLATED_IN_LYMPHOMA_TCL1, GOBP_BONE_DEVELOPMENT, GOBP_PROTEIN_MATURATION, GOBP_PROTEIN_STABILIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, chr4q22, RFX1_02, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_OSTEOCLAST_DIFFERENTIATION, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_DN

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCSER1	WWOX	Q9NZC7	446
CCSER1	NAALADL2	Q58DX5	444
CCSER1	LCORL	Q8N3X6	416
CCSER1	TIGD2	Q4W5G0	416
CCSER1	KCNIP4	Q6PIL6	411
CCSER1	GPRIN3	Q6ZVF9	402
CCSER1	MACROD2	A1Z1Q3	399
CCSER1	IMMP2L	Q96T52	398
CCSER1	FHIT	P49789	398
CCSER1	GRID2	O43424	396
CCSER1	MMRN1	Q13201	394
CCSER1	FAM98C	Q17RN3	368
CCSER1	KRABD2	Q6ZNG9	368
CCSER1	PDE4D	Q08499	367
CCSER1	CYB5R4	Q7L1T6	353

IntAct

17 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
NDEL1	OFD1	psi-mi:“MI:0914”(association)	0.530
NDEL1	SHTN1	psi-mi:“MI:0914”(association)	0.350
CCSER1	SMYD2	psi-mi:“MI:0914”(association)	0.350
CCSER1	RPSA2	psi-mi:“MI:0914”(association)	0.350
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAZ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270
CCSER1	NDEL1	psi-mi:“MI:0915”(physical association)	0.000
NDEL1	CCSER1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): CCSER1 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), CCSER1 (Affinity Capture-MS), CCSER1 (Affinity Capture-RNA), CCSER1 (Two-hybrid), CCSER1 (Two-hybrid), CCSER1 (Two-hybrid), CCSER1 (Two-hybrid), CCSER1 (Two-hybrid), CCSER1 (Affinity Capture-MS), CCSER1 (Proximity Label-MS), NDE1 (Affinity Capture-MS), CCSER1 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A096MK47, A2A995, A2ALU4, A4IGN8, A6NGG8, A6NMK8, B1AXH1, B2RQL2, D3ZMK9, D3ZUI5, E9Q309, O14513, O60303, O75128, Q0P5X5, Q14B48, Q1W617, Q2M1Z3, Q3UMF0, Q499V8, Q569L8, Q571I4, Q5BQN8, Q5DTX6, Q5HYW2, Q5T1N1, Q5VWT5, Q5ZJ26, Q62394, Q68DA7, Q69ZL1, Q6GQV1, Q6INC4, Q6PAC4, Q6ZRS4, Q6ZV73, Q6ZVD7, Q7TP36, Q7TS75, Q86YV5

Diamond homologs: Q1RMS0, Q3UHI0, Q8C0C4, Q9C0I3, Q9H7U1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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
Activation of BAD and translocation to mitochondria	7	380.7×	3e-16
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	335.9×	5e-16
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	335.9×	5e-16
Activation of BH3-only proteins	7	248.3×	5e-15
RHO GTPases activate PKNs	7	158.6×	1e-13
Intrinsic Pathway for Apoptosis	7	146.4×	2e-13
FOXO-mediated transcription	5	120.0×	2e-09
SARS-CoV-1-host interactions	7	87.8×	9e-12

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	122.1×	3e-08
intracellular protein localization	7	48.9×	6e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	142
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
562945	GRCh37/hg19 4q22.1-22.3(chr4:90005204-96971785)x1	Pathogenic
638111	GRCh37/hg19 4q21.21-22.1(chr4:80482400-92572499)x1	Pathogenic
146171	GRCh38/hg38 4q22.1(chr4:89537501-90291933)x1	Likely pathogenic

SpliceAI

6167 predictions. Top by Δscore:

Variant	Effect	Δscore
4:90312858:CATA:C	acceptor_loss	1.0000
4:90312860:T:G	acceptor_gain	1.0000
4:90312861:A:AG	acceptor_gain	1.0000
4:90312862:G:A	acceptor_loss	1.0000
4:90312862:G:GA	acceptor_gain	1.0000
4:90312862:GT:G	acceptor_gain	1.0000
4:90312862:GTT:G	acceptor_gain	1.0000
4:90312862:GTTC:G	acceptor_gain	1.0000
4:90313043:GTTTG:G	donor_gain	1.0000
4:90313045:TTGG:T	donor_loss	1.0000
4:90313046:TGG:T	donor_loss	1.0000
4:90313047:GGT:G	donor_loss	1.0000
4:90313048:G:A	donor_loss	1.0000
4:90313049:T:A	donor_loss	1.0000
4:90338542:GGCT:G	donor_gain	1.0000
4:90338543:GCT:G	donor_gain	1.0000
4:90400030:CTTCA:C	acceptor_loss	1.0000
4:90400031:TTCAG:T	acceptor_loss	1.0000
4:90400032:TCAG:T	acceptor_loss	1.0000
4:90400033:CAGG:C	acceptor_loss	1.0000
4:90400034:A:AG	acceptor_gain	1.0000
4:90400034:A:AT	acceptor_loss	1.0000
4:90400034:AG:A	acceptor_gain	1.0000
4:90400034:AGGAT:A	acceptor_gain	1.0000
4:90400035:G:GT	acceptor_gain	1.0000
4:90400035:GG:G	acceptor_gain	1.0000
4:90400035:GGAT:G	acceptor_gain	1.0000
4:90400035:GGATG:G	acceptor_gain	1.0000
4:90400128:TGG:T	donor_loss	1.0000
4:90400130:G:GG	donor_gain	1.0000

AlphaMissense

5904 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:90308328:T:C	L15S	0.998
4:90400082:T:C	L519P	0.998
4:90308426:A:C	S48R	0.997
4:90308428:C:A	S48R	0.997
4:90308428:C:G	S48R	0.997
4:90308438:A:C	S52R	0.997
4:90308440:C:A	S52R	0.997
4:90308440:C:G	S52R	0.997
4:90815832:T:C	L694P	0.997
4:90308336:T:C	F18L	0.996
4:90308338:C:A	F18L	0.996
4:90308338:C:G	F18L	0.996
4:90400088:T:C	L521P	0.996
4:90308334:T:A	I17K	0.995
4:90628192:T:A	V631D	0.995
4:90815802:T:C	L684P	0.995
4:90308319:T:A	V12D	0.994
4:90308337:T:C	F18S	0.994
4:90308331:C:A	P16Q	0.993
4:90313042:A:C	S502R	0.993
4:90313044:T:A	S502R	0.993
4:90313044:T:G	S502R	0.993
4:90400043:T:C	L506S	0.993
4:90628196:G:C	K632N	0.993
4:90628196:G:T	K632N	0.993
4:90628204:T:C	L635S	0.993
4:90308341:A:C	R19S	0.992
4:90308341:A:T	R19S	0.992
4:90308447:A:C	S55R	0.992
4:90308449:C:A	S55R	0.992

dbSNP variants (sampled 300 via entrez): RS1000001136 (4:90386390 T>A), RS1000004557 (4:90382096 A>G), RS1000004927 (4:91396266 TGAA>T), RS1000005293 (4:90659081 G>A), RS1000005604 (4:91464092 G>C), RS1000006698 (4:91151893 C>A,T), RS10000079 (4:90947340 G>A,C,T), RS1000010779 (4:90836434 TC>T), RS10000109 (4:90446118 A>G,T), RS1000011227 (4:91058691 A>C), RS1000013298 (4:90141997 G>A), RS1000013902 (4:91497698 A>T), RS1000014855 (4:90875807 C>G), RS1000018630 (4:90259744 A>G), RS1000022002 (4:91183835 G>A)

Disease associations

OMIM: gene MIM:618934 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary amenorrhea (MONDO:1060208)

Orphanet (0):

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST001651_33	Response to amphetamines	3.000000e-06
GCST001817_6	Metabolite levels (HVA-5-HIAA Factor score)	4.000000e-06
GCST001824_7	Metabolite levels (HVA)	2.000000e-06
GCST002058_9	DNA methylation (variation)	3.000000e-08
GCST002337_108	Amyotrophic lateral sclerosis (sporadic)	6.000000e-06
GCST002596_2	Colorectal cancer (calcium intake interaction)	2.000000e-06
GCST004136_7	Methadone dose in opioid dependence	3.000000e-06
GCST004956_3	Risky sexual behaviors (alcohol dependence interaction)	8.000000e-10
GCST007666_7	Depressive symptom improvement	1.000000e-06
GCST007667_2	Treatment resistant depression	2.000000e-06
GCST007879_1	Chronic kidney disease	2.000000e-08
GCST008152_54	Weight	1.000000e-06
GCST008162_10	Hip circumference	2.000000e-06
GCST009159_1	Blood protein levels	1.000000e-09
GCST010241_328	Apolipoprotein A1 levels	3.000000e-08
GCST010242_53	HDL cholesterol levels	3.000000e-09
GCST010396_110	Gut microbiota (bacterial taxa, hurdle binary method)	6.000000e-07
GCST010396_2	Gut microbiota (bacterial taxa, hurdle binary method)	9.000000e-06
GCST010396_291	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-08
GCST011983_7	Fasting glucose	3.000000e-06
GCST012170_9	Cognitive function in longevity	5.000000e-06
GCST90000047_92	Age at first sexual intercourse	7.000000e-10

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0005131	HVA measurement
EFO:0005132	5-HIAA measurement
EFO:0022599	DNA methylation
EFO:0006521	calcium intake measurement
EFO:0007907	methadone dose measurement
EFO:0007006	depressive symptom measurement
EFO:0009854	treatment resistant depression
EFO:0004338	body weight
EFO:0004747	protein measurement
EFO:0010242	beta globulin measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007874	gut microbiome measurement
EFO:0008354	cognitive function measurement
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	3
Valproic Acid	affects cotreatment, increases expression, decreases methylation	3
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	increases expression	1
benzo(e)pyrene	affects methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Cocaine	affects response to substance	1
Malathion	increases expression	1
Methapyrilene	affects methylation	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SH57	HAP1 CCSER1 (-) 1	Cancer cell line	Male
CVCL_XM56	HAP1 CCSER1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice