CCER1

Summary

CCER1 (coiled-coil glutamate rich protein 1, HGNC:28373) is a protein-coding gene on chromosome 12q21.33, encoding Coiled-coil domain-containing glutamate-rich protein 1 (Q8TC90). Regulator of histone epigenetic modifications and chromatin compaction into the sperm head, required for histone-to-protamine (HTP) transition.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_152638

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28373
Approved symbol	CCER1
Name	coiled-coil glutamate rich protein 1
Location	12q21.33
Locus type	gene with protein product
Status	Approved
Aliases	MGC26598
Ensembl gene	ENSG00000197651
Ensembl biotype	protein_coding
OMIM	620881
Entrez	196477

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000358859, ENST00000548187, ENST00000549707

RefSeq mRNA: 1 — MANE Select: NM_152638 NM_152638

CCDS: CCDS9036

Canonical transcript exons

ENST00000358859 — 1 exons

Exon	Start	End
ENSE00001409306	90952215	90955176

Expression profiles

Bgee: expression breadth broad, 27 present calls, max score 94.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0978 / max 110.5158, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132529	0.0978	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	94.04	gold quality
left testis	UBERON:0004533	93.06	gold quality
right testis	UBERON:0004534	92.82	gold quality
testis	UBERON:0000473	90.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.53	gold quality
adult organism	UBERON:0007023	76.66	gold quality
kidney epithelium	UBERON:0004819	73.41	gold quality
cardiac muscle of right atrium	UBERON:0003379	69.32	gold quality
left ventricle myocardium	UBERON:0006566	69.15	gold quality
epithelial cell of pancreas	CL:0000083	68.68	gold quality
upper arm skin	UBERON:0004263	68.24	gold quality
esophagus squamous epithelium	UBERON:0006920	64.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	64.12	gold quality
tendon of biceps brachii	UBERON:0008188	63.54	gold quality
myocardium	UBERON:0002349	58.22	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	57.28	gold quality
mucosa of sigmoid colon	UBERON:0004993	56.13	gold quality
biceps brachii	UBERON:0001507	56.11	gold quality
Brodmann (1909) area 46	UBERON:0006483	55.57	gold quality
jejunal mucosa	UBERON:0000399	55.34	gold quality
colonic mucosa	UBERON:0000317	54.22	gold quality
quadriceps femoris	UBERON:0001377	54.18	gold quality
nasal cavity epithelium	UBERON:0005384	54.13	gold quality
vastus lateralis	UBERON:0001379	53.84	gold quality
vena cava	UBERON:0004087	53.67	gold quality
pancreatic ductal cell	CL:0002079	53.24	silver quality
epithelium of nasopharynx	UBERON:0001951	53.21	gold quality
lower lobe of lung	UBERON:0008949	53.13	silver quality
cauda epididymis	UBERON:0004360	52.28	gold quality
corpus epididymis	UBERON:0004359	52.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting CCER1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-3915	99.45	68.49	1905

Literature-anchored findings (GeneRIF, showing 1)

• Phase-separated CCER1 coordinates the histone-to-protamine transition and male fertility. (PMID:38081819)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ccer1	ENSMUSG00000047025
rattus_norvegicus	Ccer1	ENSRNOG00000004875

Protein

Protein identifiers

Coiled-coil domain-containing glutamate-rich protein 1 — Q8TC90 (reviewed: Q8TC90)

All UniProt accessions (2): H0YHB9, Q8TC90

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of histone epigenetic modifications and chromatin compaction into the sperm head, required for histone-to-protamine (HTP) transition. HTP is a key event in which somatic histones are first replaced by testis-specific histone variants, then transition proteins (TNPs) are incorporated into the spermatid nucleus, and finally protamines (PRMs) replace the TNPs to promote chromatin condensation.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_689851* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027889	CCER1	Family
IPR052696	Coiled-coil_domain	Family

Pfam: PF15482

UniProt features (15 total): region of interest 4, compositionally biased region 4, sequence variant 4, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TC90-F1	50.34	0.06

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): GOBP_MALE_GAMETE_GENERATION, HATADA_METHYLATED_IN_LUNG_CANCER_DN, chr12q21, GOBP_NUCLEUS_ORGANIZATION, E4F1_Q6, HNF4_01, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_SPERMATID_NUCLEUS_DIFFERENTIATION, VDR_Q3, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GCCNNNWTAAR_UNKNOWN, MYC_Q2, ATAAGCT_MIR21, MIKKELSEN_ES_ICP_WITH_H3K4ME3_AND_H3K27ME3, GOBP_SPERM_DNA_CONDENSATION

GO Biological Process (3): spermatogenesis (GO:0007283), sperm DNA condensation (GO:0035092), cell differentiation (GO:0030154)

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

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	1
male gamete generation	1
chromatin organization	1
spermatid nucleus differentiation	1
cellular developmental process	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCER1	CIMIP4	O43247	642
CCER1	MORN5	Q5VZ52	594
CCER1	GARIN5A	Q6IPT2	507
CCER1	OR2T29	Q8NH02	505
CCER1	PEBP4	Q96S96	471
CCER1	OR5H2	Q8NGV7	447
CCER1	OR2M4	Q96R27	446
CCER1	F2Z2I4	F2Z2I4	445
CCER1	DEFB130A	P0DP74	438
CCER1	GARIN1B	Q96KD3	415
CCER1	PRAMEF2	O60811	412
CCER1	TMCO5A	Q8N6Q1	401
CCER1	OR7D4	Q8NG98	391
CCER1	CCDC192	P0DO97	390
CCER1	MORN3	Q6PF18	388

IntAct

39 interactions, top by confidence:

A	B	Type	Score
NOTCH2NLA	CCER1	psi-mi:“MI:0915”(physical association)	0.670
	CCER1	psi-mi:“MI:0915”(physical association)	0.560
CCER1	KRT31	psi-mi:“MI:0915”(physical association)	0.560
KRT40	CCER1	psi-mi:“MI:0915”(physical association)	0.560
KRT31	CCER1	psi-mi:“MI:0915”(physical association)	0.560
CCER1	KRT40	psi-mi:“MI:0915”(physical association)	0.560
CCER1		psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	CCER1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	CCER1	psi-mi:“MI:0915”(physical association)	0.560
CCER1	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	CCER1	psi-mi:“MI:0915”(physical association)	0.560
CCER1	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	CCER1	psi-mi:“MI:0915”(physical association)	0.560
CCER1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
PLSCR1	CCER1	psi-mi:“MI:0915”(physical association)	0.550
MDFI	CCER1	psi-mi:“MI:0915”(physical association)	0.370
RBPMS	CCER1	psi-mi:“MI:0915”(physical association)	0.370
CCER1	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.000
CCER1	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
CCER1	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): CCER1 (Two-hybrid), CCER1 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), CCER1 (Two-hybrid), CCER1 (Two-hybrid), CCER1 (Two-hybrid), CCER1 (Two-hybrid), CCER1 (Two-hybrid), KRTAP9-3 (Two-hybrid), KRTAP6-3 (Two-hybrid), KRTAP4-2 (Two-hybrid), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid), CCER1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GVQ3, A1A519, A6NMN3, A6QQS3, A7XCE8, D3ZAP3, E9PXT9, F1N8V3, O08550, O35668, O73823, P0C7A2, P0C7M4, P25483, P54256, P54257, Q01538, Q08050, Q0P670, Q2T9P9, Q32LN6, Q32MG2, Q5BI31, Q5REX1, Q5VWQ0, Q60542, Q64318, Q66LM5, Q66LM6, Q6AXV6, Q6NWJ0, Q6ZVD7, Q7Z2Y5, Q80T69, Q80YD3, Q8BJS7, Q8CCG1, Q8IV76, Q8NA61, Q8NA70

Diamond homologs: Q2T9P9, Q6AY45, Q8TC90, Q9CQL2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

237 predictions. Top by Δscore:

Variant	Effect	Δscore
12:90953679:T:TA	donor_gain	0.9600
12:90953680:C:A	donor_gain	0.9100
12:90953701:CCAGG:C	donor_gain	0.9000
12:90952920:C:CC	acceptor_gain	0.8600
12:90954992:C:CC	acceptor_gain	0.8100
12:90952918:CA:C	acceptor_gain	0.7900
12:90954988:GGGGC:G	acceptor_gain	0.7900
12:90954987:TGGGG:T	acceptor_gain	0.7800
12:90955131:C:CA	donor_gain	0.7600
12:90953709:T:TA	donor_gain	0.7500
12:90952915:TAGCA:T	acceptor_gain	0.7300
12:90953715:T:TA	donor_gain	0.7200
12:90954991:GC:G	acceptor_loss	0.7200
12:90954993:T:C	acceptor_loss	0.7200
12:90953578:T:C	donor_gain	0.7100
12:90954988:GGGG:G	acceptor_gain	0.7100
12:90953775:TCG:T	donor_gain	0.7000
12:90954990:GG:G	acceptor_gain	0.7000
12:90954994:G:C	acceptor_loss	0.6800
12:90955118:GTTAC:G	donor_loss	0.6800
12:90955119:TTA:T	donor_loss	0.6800
12:90955120:TACC:T	donor_loss	0.6800
12:90955121:ACC:A	donor_loss	0.6800
12:90955122:C:A	donor_loss	0.6800
12:90955123:C:A	donor_loss	0.6800
12:90953658:T:TA	donor_gain	0.6700
12:90954991:GCT:G	acceptor_gain	0.6700
12:90955117:AGTT:A	donor_loss	0.6600
12:90954989:GGGC:G	acceptor_gain	0.6100
12:90954996:G:GC	acceptor_gain	0.6000

AlphaMissense

2672 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:90954167:G:C	F192L	0.996
12:90954167:G:T	F192L	0.996
12:90954169:A:G	F192L	0.996
12:90954168:A:G	F192S	0.987
12:90954161:C:A	M194I	0.986
12:90954161:C:G	M194I	0.986
12:90954161:C:T	M194I	0.986
12:90954165:A:C	I193S	0.985
12:90954165:A:G	I193T	0.983
12:90954165:A:T	I193N	0.981
12:90954168:A:C	F192C	0.976
12:90954156:T:G	Q196P	0.972
12:90954162:A:G	M194T	0.971
12:90954153:A:C	I197S	0.964
12:90954153:A:G	I197T	0.961
12:90954177:G:A	T189I	0.951
12:90954159:T:A	N195I	0.941
12:90954169:A:T	F192I	0.940
12:90954174:G:A	T190I	0.940
12:90954140:C:A	M201I	0.936
12:90954140:C:G	M201I	0.936
12:90954140:C:T	M201I	0.936
12:90954170:T:A	Q191H	0.934
12:90954170:T:G	Q191H	0.934
12:90954141:A:G	M201T	0.928
12:90954144:T:A	D200V	0.927
12:90954179:G:C	N188K	0.927
12:90954179:G:T	N188K	0.927
12:90954169:A:C	F192V	0.924
12:90954145:C:G	D200H	0.918

dbSNP variants (sampled 300 via entrez): RS1000038557 (12:90955320 T>C), RS1000713090 (12:90952799 G>A), RS1001102676 (12:90952404 A>G), RS1001439686 (12:90955882 A>G), RS1003809395 (12:90954628 G>T), RS1004729720 (12:90953540 T>G), RS1006289318 (12:90955643 A>G), RS1007485841 (12:90956327 GTTTCATTATA>G), RS1007710238 (12:90956439 T>G), RS1007742794 (12:90956727 A>G), RS1008230206 (12:90955501 G>A), RS1008243570 (12:90953485 T>A), RS1008346110 (12:90955351 G>C), RS1009713698 (12:90957117 T>C), RS1010189721 (12:90955354 G>A,C)

Disease associations

OMIM: gene MIM:620881 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003996_9	Monobrow	2.000000e-12
GCST007565_169	Morning person	1.000000e-14
GCST007565_25	Morning person	5.000000e-16
GCST007576_60	Chronotype	5.000000e-16
GCST010989_45	Body size at age 10	9.000000e-09
GCST012490_372	Femur bone mineral density x serum urate levels interaction	3.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007906	synophrys measurement
EFO:0008328	chronotype measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol S	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Valproic Acid	increases methylation	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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