MMP23B

Summary

MMP23B (matrix metallopeptidase 23B, HGNC:7171) is a protein-coding gene on chromosome 1p36.33, encoding Matrix metalloproteinase-23 (O75900). Protease.

This gene (MMP23B) encodes a member of the matrix metalloproteinase (MMP) family, and it is part of a duplicated region of chromosome 1p36.3. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. This gene belongs to the more telomeric copy of the duplicated region.

Source: NCBI Gene 8510 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 31 total
• Phenotypes (HPO): 99
• MANE Select transcript: NM_006983

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7171
Approved symbol	MMP23B
Name	matrix metallopeptidase 23B
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Aliases	MIFR, MIFR-1
Ensembl gene	ENSG00000189409
Ensembl biotype	protein_coding
OMIM	603321
Entrez	8510

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000356026, ENST00000378675, ENST00000435358, ENST00000472264, ENST00000479814, ENST00000486400, ENST00000489782, ENST00000490017, ENST00000503792, ENST00000512731, ENST00000891264, ENST00000891265, ENST00000936716

RefSeq mRNA: 1 — MANE Select: NM_006983 NM_006983

CCDS: CCDS30559

Canonical transcript exons

ENST00000356026 — 8 exons

Exon	Start	End
ENSE00001765095	1632783	1632913
ENSE00001927041	1632173	1632374
ENSE00003464913	1632981	1633120
ENSE00003510374	1634202	1634328
ENSE00003520085	1633989	1634099
ENSE00003557679	1633188	1633355
ENSE00003567941	1633748	1633912
ENSE00003691124	1634451	1634654

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 98.29.

FANTOM5 (CAGE): breadth broad, TPM avg 4.1328 / max 295.1490, expressed in 464 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141	2.8082	391
139	0.4619	211
140	0.3541	188
136	0.2131	77
142	0.1512	89
138	0.0766	39
137	0.0677	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.29	gold quality
right ovary	UBERON:0002118	95.85	gold quality
left uterine tube	UBERON:0001303	95.57	gold quality
right coronary artery	UBERON:0001625	95.25	gold quality
left ovary	UBERON:0002119	94.79	gold quality
heart left ventricle	UBERON:0002084	94.27	gold quality
thoracic aorta	UBERON:0001515	94.22	gold quality
ascending aorta	UBERON:0001496	94.19	gold quality
descending thoracic aorta	UBERON:0002345	94.12	gold quality
ovary	UBERON:0000992	93.47	gold quality
granulocyte	CL:0000094	93.13	gold quality
left coronary artery	UBERON:0001626	92.58	gold quality
heart	UBERON:0000948	91.17	gold quality
myometrium	UBERON:0001296	91.00	gold quality
body of uterus	UBERON:0009853	89.25	gold quality
right lung	UBERON:0002167	88.21	gold quality
right atrium auricular region	UBERON:0006631	88.09	gold quality
mucosa of stomach	UBERON:0001199	87.60	gold quality
upper lobe of left lung	UBERON:0008952	87.33	gold quality
placenta	UBERON:0001987	86.77	gold quality
endocervix	UBERON:0000458	85.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.67	gold quality
omental fat pad	UBERON:0010414	85.38	gold quality
fundus of stomach	UBERON:0001160	84.66	gold quality
prostate gland	UBERON:0002367	84.41	gold quality
pituitary gland	UBERON:0000007	84.35	gold quality
vagina	UBERON:0000996	84.07	gold quality
lung	UBERON:0002048	84.05	gold quality
ectocervix	UBERON:0012249	83.79	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	83.71	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	593.98
E-MTAB-6701	yes	67.13
E-HCAD-10	yes	35.56
E-ANND-3	yes	7.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF20

Literature-anchored findings (GeneRIF, showing 2)

• Compares rat and human proteins, describes unique Type II membrane topology, and suggests a role in reproductive processes. (PMID:11328856)
• There is evidence of MMP23B secretion in plasma and urine, suggesting a role of this poorly characterized metalloproteinase in urinary bladder cancer as a potential non-invasive biomarker for this cancer (PMID:30052775)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	MMP23B	ENSDARG00000043079
mus_musculus	Mmp23	ENSMUSG00000029061
rattus_norvegicus	Mmp23	ENSRNOG00000017477
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00194737

Paralogs (23): MMP25 (ENSG00000008516), MMP2 (ENSG00000087245), MMP11 (ENSG00000099953), MMP9 (ENSG00000100985), MMP15 (ENSG00000102996), HPX (ENSG00000110169), MMP8 (ENSG00000118113), MMP19 (ENSG00000123342), MMP24 (ENSG00000125966), MMP7 (ENSG00000137673), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Matrix metalloproteinase-23 — O75900 (reviewed: O75900)

Alternative names: Femalysin, MIFR-1, Matrix metalloproteinase-21, Matrix metalloproteinase-22

All UniProt accessions (8): B4DMZ6, D6REP6, O75900, H0Y6I4, H0YA69, H0YAE5, J3KRS4, O75086

UniProt curated annotations — full annotation on UniProt →

Function. Protease. May regulate the surface expression of some potassium channels by retaining them in the endoplasmic reticulum.

Subcellular location. Endoplasmic reticulum membrane. Membrane.

Tissue specificity. Predominantly expressed in ovary, testis and prostate.

Post-translational modifications. N-glycosylated. Proteolytic cleavage might yield an active form.

Activity regulation. Inhibited by TIMP2.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The ShKT domain associates with, and blocks several potassium channels in the nanomolar to low micromolar range. The relative affinity is Kv1.6 > Kv1.3 > Kv1.1 = Kv3.2 > Kv1.4.

Similarity. Belongs to the peptidase M10A family.

Isoforms (3)

UniProt ID	Names	Canonical?
O75900-1	1, MMP21/22A	yes
O75900-2	2, MMP21/22B
O75900-3	3, MMP21/22C

RefSeq proteins (1): NP_008914* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001818	Pept_M10_metallopeptidase	Domain
IPR003582	ShKT_dom	Domain
IPR003599	Ig_sub	Domain
IPR006026	Peptidase_Metallo	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR021190	Pept_M10A	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR033739	M10A_MMP	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF00413, PF01549

UniProt features (25 total): glycosylation site 4, disulfide bond 4, binding site 3, chain 2, splice variant 2, topological domain 2, domain 2, propeptide 1, site 1, sequence variant 1, mutagenesis site 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75900-F1	77.36	0.44

Functional residue map

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

Catalytic / active sites (2): 78–79 (cleavage; by furin-like protease); 212

Ligand- & substrate-binding residues (3): 215; 221; 211

Disulfide bonds (4): 255–289, 262–282, 271–286, 321–370

Glycosylation sites (4): 92, 148, 232, 316

Mutagenesis-validated functional residues (1):

Position	Phenotype
78	abolishes processing of soluble form.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 292 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, USF_C, GATA6_01, GATA1_04, GATA1_03, CUI_TCF21_TARGETS_2_DN, GATA_Q6, WGGAATGY_TEF1_Q6, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOBP_PROTEOLYSIS, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_PEPTIDASE_ACTIVITY, ARNT_01, YOSHIMURA_MAPK8_TARGETS_UP, CHEN_METABOLIC_SYNDROM_NETWORK

GO Biological Process (3): proteolysis (GO:0006508), extracellular matrix organization (GO:0030198), collagen catabolic process (GO:0030574)

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), endoplasmic reticulum membrane (GO:0005789), extracellular matrix (GO:0031012), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
collagen metabolic process	1
endopeptidase activity	1
metallopeptidase activity	1
peptidase activity	1
transition metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
external encapsulating structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMP23B	CDK13	Q14004	930
MMP23B	CDK11A	Q9UQ88	861
MMP23B	CDK11B	P21127	858
MMP23B	HPX	P02790	792
MMP23B	FURIN	P09958	648
MMP23B	TIMP2	P16035	502
MMP23B	TIMP4	Q99727	500
MMP23B	MMP19	Q99542	496
MMP23B	TIMP1	P01033	476
MMP23B	TIMP3	P35625	461
MMP23B	FN1	P02751	380
MMP23B	CARMIL1	Q5VZK9	378
MMP23B	CCL7	P80098	373
MMP23B	IL1R1	P14778	369
MMP23B	CFAP52	Q8N1V2	354

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MMP23B	GLRX	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): MMP23B (Biochemical Activity), MMP23B (Negative Genetic), MMP23B (Two-hybrid)

ESM2 similar proteins: A5D8T8, O35217, O75078, O75882, O75900, O88272, O88507, O88676, O95633, P08887, P0C7M8, P0C7M9, P26992, P78539, Q00961, Q01098, Q08406, Q0ZCA7, Q14957, Q1LZB9, Q2TBM7, Q4V7F2, Q5EA46, Q5VV63, Q63769, Q642A6, Q6A051, Q6IA17, Q6P1D5, Q6PCB0, Q6UXF7, Q71DR4, Q7TNS7, Q7TSQ1, Q8NCF0, Q8R2Z5, Q8R366, Q91XD7, Q96FT7, Q96HD1

Diamond homologs: A0A0N9E2K8, D0EM77, G5EBU3, O04529, O54732, O55761, O75900, O88272, O88676, O93470, P04004, P22458, P22757, P41245, P48819, P50280, P51511, P53690, P55032, Q02853, Q10739, Q196W5, Q2TBM7, Q499S5, Q5XF51, Q8K3F2, Q8N119, Q90YC2, Q99542, Q9NRE1, O13065, O18733, O18767, O18927, O23507, O35548, O44836, O55123, O60882, O62806

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MMP23B	up-regulates	ECM_disassembly
MMP23B	down-regulates	ECM

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

936 predictions. Top by Δscore:

Variant	Effect	Δscore
1:1632375:GTG:G	donor_loss	1.0000
1:1633116:GA:G	donor_gain	1.0000
1:1633348:G:GT	donor_gain	1.0000
1:1633747:GGC:G	acceptor_gain	1.0000
1:1633910:ACGGT:A	donor_loss	1.0000
1:1633911:CGG:C	donor_loss	1.0000
1:1633914:T:A	donor_loss	1.0000
1:1634321:A:T	donor_gain	1.0000
1:1634324:GTGTA:G	donor_gain	1.0000
1:1632371:GCAG:G	donor_gain	0.9900
1:1632375:G:GG	donor_gain	0.9900
1:1632778:T:TA	acceptor_gain	0.9900
1:1632975:CTGCA:C	acceptor_loss	0.9900
1:1632976:TGCA:T	acceptor_loss	0.9900
1:1632977:GCA:G	acceptor_loss	0.9900
1:1632978:CA:C	acceptor_loss	0.9900
1:1632979:A:AG	acceptor_gain	0.9900
1:1632979:A:C	acceptor_loss	0.9900
1:1632979:AG:A	acceptor_gain	0.9900
1:1632980:G:GG	acceptor_gain	0.9900
1:1632980:GG:G	acceptor_gain	0.9900
1:1632980:GGAT:G	acceptor_gain	0.9900
1:1632980:GGATC:G	acceptor_gain	0.9900
1:1632997:C:CA	acceptor_gain	0.9900
1:1632998:G:A	acceptor_gain	0.9900
1:1633117:A:G	donor_gain	0.9900
1:1633311:GCGA:G	donor_gain	0.9900
1:1633312:C:T	donor_gain	0.9900
1:1633352:AAAG:A	donor_loss	0.9900
1:1633353:AAGGT:A	donor_loss	0.9900

AlphaMissense

2493 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:1632890:G:C	W88C	0.998
1:1632890:G:T	W88C	0.998
1:1633190:T:C	F144L	0.998
1:1633192:C:A	F144L	0.998
1:1633192:C:G	F144L	0.998
1:1633241:T:C	F161L	0.998
1:1633242:T:G	F161C	0.998
1:1633243:C:A	F161L	0.998
1:1633243:C:G	F161L	0.998
1:1633321:G:C	W187C	0.998
1:1633321:G:T	W187C	0.998
1:1633054:T:A	W121R	0.997
1:1633054:T:C	W121R	0.997
1:1633056:G:C	W121C	0.997
1:1633056:G:T	W121C	0.997
1:1633302:T:C	F181S	0.997
1:1634560:T:C	C370R	0.997
1:1633319:T:A	W187R	0.996
1:1633319:T:C	W187R	0.996
1:1633787:A:T	E212V	0.996
1:1634554:T:G	Y368D	0.996
1:1634561:G:A	C370Y	0.996
1:1634562:C:G	C370W	0.996
1:1632909:T:G	Y95D	0.995
1:1633079:T:C	F129S	0.995
1:1633191:T:C	F144S	0.995
1:1633191:T:G	F144C	0.995
1:1633305:A:T	D182V	0.995
1:1634291:T:A	C321S	0.995
1:1634292:G:C	C321S	0.995

dbSNP variants (sampled 300 via entrez): RS1000486332 (1:1630594 A>C,T), RS1000822115 (1:1630600 C>A,G,T), RS1000934524 (1:1630689 G>A,C,T), RS1001394569 (1:1632556 C>A,G,T), RS1002000618 (1:1632038 G>A,T), RS1003099697 (1:1632237 G>A,T), RS1003213957 (1:1631704 C>T), RS1003291821 (1:1632402 C>A,T), RS1003411075 (1:1631406 C>T), RS1005035343 (1:1632418 T>G), RS1005388596 (1:1631731 C>T), RS1005442207 (1:1631875 T>C,G), RS1006952451 (1:1634989 T>C), RS1007062323 (1:1630966 G>C), RS1007177058 (1:1631053 A>T)

Disease associations

OMIM: gene MIM:603321 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

99 total (30 of 99 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000055	Abnormal female external genitalia morphology
HP:0000077	Abnormality of the kidney
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000160	Narrow mouth
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000270	Delayed cranial suture closure
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000464	Abnormality of the neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior
HP:0000717	Autism

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_34	Body mass index	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M10: Matrix metallopeptidase

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
mono-(2-ethylhexyl)phthalate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Cytarabine	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Valproic Acid	increases methylation	1
Isotretinoin	increases expression	1

Clinical trials (associated diseases)

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