CER1

Summary

CER1 (cerberus 1, DAN family BMP antagonist, HGNC:1862) is a protein-coding gene on chromosome 9p22.3, encoding Cerberus (O95813). Cytokine that may play a role in anterior neural induction and somite formation during embryogenesis in part through a BMP-inhibitory mechanism.

This gene encodes a cytokine member of the cysteine knot superfamily, characterized by nine conserved cysteines and a cysteine knot region. The cerberus-related cytokines, together with Dan and DRM/Gremlin, represent a group of bone morphogenetic protein (BMP) antagonists that can bind directly to BMPs and inhibit their activity.

Source: NCBI Gene 9350 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 51 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_005454

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1862
Approved symbol	CER1
Name	cerberus 1, DAN family BMP antagonist
Location	9p22.3
Locus type	gene with protein product
Status	Approved
Aliases	DAND4
Ensembl gene	ENSG00000147869
Ensembl biotype	protein_coding
OMIM	603777
Entrez	9350

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000380911

RefSeq mRNA: 1 — MANE Select: NM_005454 NM_005454

CCDS: CCDS6476

Canonical transcript exons

ENST00000380911 — 2 exons

Exon	Start	End
ENSE00001486775	14719724	14720386
ENSE00001486776	14722166	14722733

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 69.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.9668 / max 227.7916, expressed in 100 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100034	1.9668	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	69.94	silver quality
ileal mucosa	UBERON:0000331	62.91	silver quality
upper leg skin	UBERON:0004262	61.12	silver quality
pancreatic ductal cell	CL:0002079	60.15	silver quality
diaphragm	UBERON:0001103	59.78	gold quality
gluteal muscle	UBERON:0002000	59.58	gold quality
deltoid	UBERON:0001476	58.16	gold quality
mucosa of paranasal sinus	UBERON:0005030	58.13	gold quality
tendon of biceps brachii	UBERON:0008188	55.84	gold quality
skin of hip	UBERON:0001554	54.60	silver quality
quadriceps femoris	UBERON:0001377	53.65	gold quality
triceps brachii	UBERON:0001509	53.28	gold quality
vastus lateralis	UBERON:0001379	52.43	gold quality
endothelial cell	CL:0000115	51.66	gold quality
epithelial cell of pancreas	CL:0000083	51.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	50.06	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
metanephros cortex	UBERON:0010533	49.07	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
metanephros	UBERON:0000081	48.73	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	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

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	15417.47
E-GEOD-109979	yes	11083.37
E-MTAB-8060	no	65.26
E-GEOD-36552	no	40.49
E-ANND-3	no	1.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, HHEX

miRNA regulators (miRDB)

30 targeting CER1, 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-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-432-5P	98.00	68.13	989
HSA-MIR-4494	97.86	64.93	850
HSA-MIR-7112-3P	97.67	68.77	948
HSA-MIR-708-3P	97.50	68.67	1082
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-34A-3P	96.80	67.70	805

Literature-anchored findings (GeneRIF, showing 7)

• functional candidate gene for trigonocephaly (PMID:18452192)
• successful identification of an association with CER1 in humans together with our mouse study suggests that CER1 may play a role in the development of bone or its metabolism (PMID:19113921)
• CER1 gene variations play a significant role in determining BMD and vertebral or hip fractures, which might be helpful in clinical practice to identify patients with increased fracture risk (PMID:22543871)
• results show that Cer1 (or CER1) serves as a good marker for quantification of definitive endoderm differentiation of mouse and human ES/iPS cells (PMID:23717584)
• No significant association between the studied DKK1 variations and osteoporosis was found, while CER1 variations seem to play a significant role in the determination of osteoporosis, combined with bone markers, in postmenopausal osteoporotic women. (PMID:24138842)
• Cerberus binds and inhibits Nodal, Activin B, BMP-6, and BMP-7 but not BMP-2 or Activin A. (PMID:26802359)
• CER 1 gene polymorphism in postmenopausal Roma and non-Roma Slovak women in connection with osteoporosis. (PMID:34859850)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cer1	ENSMUSG00000038192
rattus_norvegicus	Cer1	ENSRNOG00000010518

Paralogs (1): DAND5 (ENSG00000179284)

Protein

Protein identifiers

Cerberus — O95813 (reviewed: O95813)

Alternative names: Cerberus-related protein, DAN domain family member 4

All UniProt accessions (1): O95813

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine that may play a role in anterior neural induction and somite formation during embryogenesis in part through a BMP-inhibitory mechanism. Can regulate Nodal signaling during gastrulation as well as the formation and patterning of the primitive streak.

Subunit / interactions. Forms monomers and predominantly dimers.

Subcellular location. Secreted.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the DAN family.

RefSeq proteins (1): NP_005445* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004133	DAN_dom	Domain
IPR006207	Cys_knot_C	Domain
IPR016860	Cerberus	Family
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF03045

UniProt features (17 total): disulfide bond 4, sequence variant 3, sequence conflict 2, region of interest 2, glycosylation site 2, signal peptide 1, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95813-F1	59.19	0.19

Functional residue map

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

Disulfide bonds (4): 186–239, 190–241, 162–209, 176–223

Glycosylation sites (2): 26, 222

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1181150	Signaling by NODAL
R-HSA-1433617	Regulation of signaling by NODAL
R-HSA-201451	Signaling by BMP
R-HSA-9937080	Developmental Lineage of Multipotent Pancreatic Progenitor Cells
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9734767	Developmental Cell Lineages
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells

MSigDB gene sets: 163 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_AXIS_SPECIFICATION, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, NKX25_02, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION, GOBP_GROWTH, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, AAAYRNCTG_UNKNOWN, GOBP_BONE_GROWTH, GOBP_DORSAL_VENTRAL_PATTERN_FORMATION, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_RESPONSE_TO_METAL_ION

GO Biological Process (22): ureteric bud development (GO:0001657), growth plate cartilage chondrocyte proliferation (GO:0003419), gastrulation (GO:0007369), nervous system development (GO:0007399), negative regulation of cell population proliferation (GO:0008285), anterior/posterior axis specification (GO:0009948), anterior/posterior pattern specification (GO:0009952), signal transduction involved in regulation of gene expression (GO:0023019), bone mineralization (GO:0030282), negative regulation of BMP signaling pathway (GO:0030514), negative regulation of activin receptor signaling pathway (GO:0032926), obsolete sequestering of BMP in extracellular matrix (GO:0035582), cell migration involved in gastrulation (GO:0042074), determination of dorsal identity (GO:0048263), determination of heart left/right asymmetry (GO:0061371), cellular response to cadmium ion (GO:0071276), negative regulation of mesoderm development (GO:2000381), regionalization (GO:0003002), cell population proliferation (GO:0008283), tissue development (GO:0009888), animal organ development (GO:0048513), system development (GO:0048731)

GO Molecular Function (4): cytokine activity (GO:0005125), morphogen activity (GO:0016015), BMP binding (GO:0036122), protein homodimerization activity (GO:0042803)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Developmental Biology	2
Developmental Cell Lineages of the Exocrine Pancreas	2
Signaling by NODAL	1
Signaling by TGFB family members	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	2
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	2
receptor ligand activity	2
mesonephric tubule development	1
growth plate cartilage development	1
ectoderm formation	1
endoderm formation	1
mesoderm formation	1
embryonic morphogenesis	1
system development	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
axis specification	1
anterior/posterior pattern specification	1
regionalization	1
signal transduction	1
regulation of gene expression	1
ossification	1
biomineral tissue development	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
activin receptor signaling pathway	1
regulation of activin receptor signaling pathway	1
ameboidal-type cell migration	1
gastrulation	1
dorsal/ventral pattern formation	1
determination of dorsal/ventral asymmetry	1
determination of left/right symmetry	1
heart development	1
response to cadmium ion	1
cellular response to metal ion	1
mesoderm development	1
negative regulation of developmental process	1
regulation of mesoderm development	1
pattern specification process	1
cellular process	1
anatomical structure development	1
cytokine binding	1
identical protein binding	1

Protein interactions and networks

STRING

698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CER1	CHP1	Q99653	755
CER1	TYRP1	P17643	720
CER1	LEFTY2	O00292	709
CER1	LEFTY1	O75610	690
CER1	NODAL	Q96S42	612
CER1	SOX17	Q9H6I2	576
CER1	MIXL1	Q9H2W2	571
CER1	FOXA2	Q9Y261	507
CER1	SOSTDC1	Q6X4U4	480
CER1	OTX2	P32243	456
CER1	BMP4	P12644	455
CER1	NFIB	O00712	452
CER1	WNT3	P56703	438
CER1	MPDZ	O75970	437
CER1	EOMES	O95936	436

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CER1	POTEF	psi-mi:“MI:0914”(association)	0.530
CER1	ADA	psi-mi:“MI:0914”(association)	0.350
CER1	PC	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): HSPA1A (Affinity Capture-MS), POTEF (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), GTPBP1 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), ADAMTS1 (Affinity Capture-MS), FN1 (Affinity Capture-MS), PPM1A (Affinity Capture-MS), CAMK1 (Affinity Capture-MS), VHL (Affinity Capture-MS), HSPA1A (Affinity Capture-MS), FN1 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), PPM1A (Affinity Capture-MS), VHL (Affinity Capture-MS)

ESM2 similar proteins: A2BDC9, A6NM62, E9Q793, O08999, O35806, O55233, O95813, P13207, P22389, P23499, P23943, P24054, P29560, P35054, P70041, P86275, Q07G34, Q14515, Q17R60, Q2Q0I9, Q3UU94, Q3V1M1, Q4V9H3, Q4ZHG4, Q5K027, Q5NRP8, Q5NRP9, Q5NRQ1, Q5QQ37, Q68CR7, Q6WRH9, Q6WRI0, Q701R2, Q701R3, Q701R4, Q76K27, Q8CG19, Q8JIR8, Q8JZQ0, Q8R1W8

Diamond homologs: O35793, O55233, O60565, O70326, O73753, O73754, O73755, O88273, O95813, P41271, P70041, Q06880, Q28H35, Q61477, Q6DF53, Q6NZ13, Q76LW6, Q800X4, Q8WNY1, Q90YC9, Q9H772, Q07G34, Q8N907, Q9PWB0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	42
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
394262	GRCh37/hg19 9p24.3-22.2(chr9:213161-17496750)x1	Pathogenic
3338458	GRCh37/hg19 9p23-22.3(chr9:13927869-15424029)x1	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1772 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:14720346:T:A	N183I	0.994
9:14720333:A:C	F187L	0.992
9:14720333:A:T	F187L	0.992
9:14720335:A:G	F187L	0.992
9:14720345:G:C	N183K	0.992
9:14720345:G:T	N183K	0.992
9:14722172:G:C	F167L	0.992
9:14722172:G:T	F167L	0.992
9:14722174:A:G	F167L	0.992
9:14720337:C:G	C186S	0.991
9:14720338:A:G	C186R	0.991
9:14720338:A:T	C186S	0.991
9:14720336:G:C	C186W	0.990
9:14722188:C:G	C162S	0.990
9:14722189:A:T	C162S	0.990
9:14722173:A:C	F167C	0.988
9:14722188:C:T	C162Y	0.988
9:14722271:C:A	W134C	0.988
9:14722271:C:G	W134C	0.988
9:14720178:C:G	C239S	0.987
9:14720179:A:T	C239S	0.987
9:14720334:A:C	F187C	0.987
9:14720340:A:G	L185P	0.987
9:14722189:A:G	C162R	0.987
9:14720337:C:T	C186Y	0.986
9:14722187:G:C	C162W	0.986
9:14720267:A:C	C209W	0.985
9:14722173:A:G	F167S	0.985
9:14720172:C:G	C241S	0.984
9:14720173:A:T	C241S	0.984

dbSNP variants (sampled 300 via entrez): RS1001225836 (9:14722786 G>A,C), RS1001852970 (9:14717419 A>C), RS1002090480 (9:14721901 C>T), RS1002862998 (9:14718435 T>C), RS1003162080 (9:14723288 T>C), RS1003408057 (9:14718679 A>T), RS1004099833 (9:14721455 G>A,T), RS1004122658 (9:14721592 G>A,T), RS1004411234 (9:14717228 T>C), RS1004865395 (9:14722851 C>G,T), RS1005134087 (9:14718404 A>T), RS1005592934 (9:14718852 C>G,T), RS1006167380 (9:14723775 A>G), RS1006169369 (9:14723611 A>C), RS1006445515 (9:14720341 G>A,T)

Disease associations

OMIM: gene MIM:603777 | disease phenotypes: MIM:618286

GenCC curated gene-disease

Mondo (1): macrocephaly, acquired, with impaired intellectual development (MONDO:0032658)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008829_11	Neuritic plaque	8.000000e-06
GCST010482_3	Cardiovascular death or myocardial infarction in response to clopidogrel treatment	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006798	neuritic plaque measurement
EFO:0006919	cardiovascular event 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
(+)-JQ1 compound	decreases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	increases expression	1
Fluorouracil	decreases expression	1
Tretinoin	affects expression	1

Clinical trials (associated diseases)

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