MPND

Summary

MPND (MPN domain containing, HGNC:25934) is a protein-coding gene on chromosome 19p13.3, encoding MPN domain-containing protein (Q8N594). Probable protease.

Predicted to enable metallopeptidase activity and polyubiquitin modification-dependent protein binding activity. Predicted to be involved in double-strand break repair. Predicted to be part of BRCA1-A complex and BRISC complex.

Source: NCBI Gene 84954 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 112 total
• MANE Select transcript: NM_001300862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25934
Approved symbol	MPND
Name	MPN domain containing
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14981
Ensembl gene	ENSG00000008382
Ensembl biotype	protein_coding
Entrez	84954

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 nonsense_mediated_decay

ENST00000262966, ENST00000359935, ENST00000594162, ENST00000594716, ENST00000596722, ENST00000597036, ENST00000599840, ENST00000601877, ENST00000927551, ENST00000964906, ENST00000964907, ENST00000964908, ENST00000964909, ENST00000964910

RefSeq mRNA: 3 — MANE Select: NM_001300862 NM_001159846, NM_001300862, NM_032868

CCDS: CCDS42470, CCDS54200, CCDS74261

Canonical transcript exons

ENST00000599840 — 13 exons

Exon	Start	End
ENSE00000361069	4354045	4354129
ENSE00000664087	4345745	4345981
ENSE00000664090	4352897	4353029
ENSE00000664094	4355097	4355173
ENSE00000664098	4358083	4358172
ENSE00000868749	4359163	4359255
ENSE00000868751	4357515	4357585
ENSE00000868752	4357253	4357421
ENSE00000868753	4354949	4355021
ENSE00000868754	4354324	4354420
ENSE00001208144	4343708	4343994
ENSE00003057225	4359916	4360078
ENSE00003173924	4343562	4343600

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 93.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0935 / max 163.1378, expressed in 1761 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173336	4.6226	1682
173337	2.1938	807
173335	1.2771	495

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	93.68	gold quality
ileal mucosa	UBERON:0000331	92.47	gold quality
right lobe of liver	UBERON:0001114	90.89	gold quality
apex of heart	UBERON:0002098	90.61	gold quality
anterior cingulate cortex	UBERON:0009835	89.51	gold quality
right frontal lobe	UBERON:0002810	89.15	gold quality
prefrontal cortex	UBERON:0000451	88.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.36	gold quality
transverse colon	UBERON:0001157	87.89	gold quality
lower esophagus mucosa	UBERON:0035834	87.36	gold quality
right adrenal gland cortex	UBERON:0035827	87.33	gold quality
right adrenal gland	UBERON:0001233	87.05	gold quality
cortical plate	UBERON:0005343	86.73	gold quality
granulocyte	CL:0000094	86.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.35	gold quality
monocyte	CL:0000576	86.26	gold quality
left adrenal gland cortex	UBERON:0035825	86.20	gold quality
leukocyte	CL:0000738	86.12	gold quality
left adrenal gland	UBERON:0001234	86.05	gold quality
amygdala	UBERON:0001876	85.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.90	gold quality
ganglionic eminence	UBERON:0004023	85.60	gold quality
body of stomach	UBERON:0001161	85.53	gold quality
duodenum	UBERON:0002114	85.44	gold quality
neocortex	UBERON:0001950	85.40	gold quality
liver	UBERON:0002107	85.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.27	gold quality
sural nerve	UBERON:0015488	85.09	gold quality
frontal cortex	UBERON:0001870	84.97	gold quality
colon	UBERON:0001155	84.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.60

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mpnd	ENSDARG00000061989
mus_musculus	Mpnd	ENSMUSG00000003199
rattus_norvegicus	Mpnd	ENSRNOG00000048282

Paralogs (3): SMARCC2 (ENSG00000139613), MYSM1 (ENSG00000162601), SMARCC1 (ENSG00000173473)

Protein

Protein identifiers

MPN domain-containing protein — Q8N594 (reviewed: Q8N594)

All UniProt accessions (7): Q8N594, M0QXC4, M0QXK5, M0R044, M0R0F2, M0R189, W4VSR2

UniProt curated annotations — full annotation on UniProt →

Function. Probable protease. Acts as a sensor of N(6)-methyladenosine methylation on DNA (m6A): recognizes and binds m6A DNA, leading to its degradation. Binds only double strand DNA (dsDNA) in a sequence-independent manner.

Subunit / interactions. Monomer. Mainly monomoric, but when binds to dsDNA, forms homotetramer assembled into two homodimers. May interact with histones; this interaction is facilitated by dsDNA binding.

Post-translational modifications. Degraded following binding to N(6)-methyladenosine methylated DNA (m6A).

Domain organisation. The RAMA domain recognizes and binds N(6)-methyladenosine methylation on DNA (m6A). The RAMA domain mediates interaction with histones. The two acidic regions inhibit DNA binding. The two acidic regions promotes histone interaction.

Similarity. Belongs to the peptidase M67 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N594-1	1	yes
Q8N594-2	2

RefSeq proteins (3): NP_001153318, NP_001287791, NP_116257 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000555	JAMM/MPN+_dom	Domain
IPR037518	MPN	Domain
IPR040843	RAMA	Domain
IPR050242	JAMM_MPN+_peptidase_M67A	Family

Pfam: PF01398, PF18755

UniProt features (24 total): binding site 6, compositionally biased region 4, modified residue 4, domain 2, splice variant 2, region of interest 2, initiator methionine 1, chain 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N594-F1	72.14	0.30

Functional residue map

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

Ligand- & substrate-binding residues (6): 123; 125; 145; 349; 351; 362

Post-translational modifications (4): 2, 8, 178, 181

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_DNA_DAMAGE_RESPONSE, GOBP_PROTEOLYSIS, chr19p13, GOBP_DNA_METABOLIC_PROCESS, GOMF_PEPTIDASE_ACTIVITY, GOBP_DNA_REPAIR, GOMF_UBIQUITIN_LIKE_PROTEIN_PEPTIDASE_ACTIVITY, CHEN_METABOLIC_SYNDROM_NETWORK, GOCC_BRCA1_A_COMPLEX, GOCC_BRISC_COMPLEX, GOMF_POLYUBIQUITIN_MODIFICATION_DEPENDENT_PROTEIN_BINDING, GOMF_MODIFICATION_DEPENDENT_PROTEIN_BINDING

GO Biological Process (2): double-strand break repair (GO:0006302), proteolysis (GO:0006508)

GO Molecular Function (7): metallopeptidase activity (GO:0008237), polyubiquitin modification-dependent protein binding (GO:0031593), metal ion binding (GO:0046872), metal-dependent deubiquitinase activity (GO:0140492), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (2): BRCA1-A complex (GO:0070531), BRISC complex (GO:0070552)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear protein-containing complex	2
DNA repair	1
protein metabolic process	1
peptidase activity	1
modification-dependent protein binding	1
cation binding	1
metallopeptidase activity	1
deubiquitinase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1

Protein interactions and networks

STRING

2238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPND	COPS6	Q7L5N1	680
MPND	JOSD2	Q8TAC2	647
MPND	COPS5	Q92905	645
MPND	JOSD1	Q15040	638
MPND	STAMBPL1	Q96FJ0	612
MPND	ATXN3L	Q9H3M9	578
MPND	EIF3C	Q99613	569
MPND	EIF3F	O00303	557
MPND	ATXN3	P54252	555
MPND	ZUP1	Q96AP4	540
MPND	STAMBP	O95630	521
MPND	MINDY1	Q8N5J2	513
MPND	PSMD14	O00487	507
MPND	EIF3H	O15372	472
MPND	PSMD7	P51665	471

IntAct

73 interactions, top by confidence:

A	B	Type	Score
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
DCTN1	MPND	psi-mi:“MI:0915”(physical association)	0.560
DMWD	MPND	psi-mi:“MI:0915”(physical association)	0.560
	MPND	psi-mi:“MI:0915”(physical association)	0.560
HOXD10	MPND	psi-mi:“MI:0915”(physical association)	0.560
MPND	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
NF2	MPND	psi-mi:“MI:0915”(physical association)	0.560
NOS3	MPND	psi-mi:“MI:0915”(physical association)	0.560
PRKN	MPND	psi-mi:“MI:0915”(physical association)	0.560
MPND	PRPS1	psi-mi:“MI:0915”(physical association)	0.560
MPND	WFS1	psi-mi:“MI:0915”(physical association)	0.560
KIF1B	MPND	psi-mi:“MI:0915”(physical association)	0.560
RNF11	MPND	psi-mi:“MI:0915”(physical association)	0.560
MPND	HTRA2	psi-mi:“MI:0915”(physical association)	0.560
MPND	JPH3	psi-mi:“MI:0915”(physical association)	0.560
MPND	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
SOD1	MPND	psi-mi:“MI:0915”(physical association)	0.560
APP	MPND	psi-mi:“MI:0915”(physical association)	0.560
SNCA	MPND	psi-mi:“MI:0915”(physical association)	0.560
HTT	MPND	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	MPND	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	MPND	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (19): MPND (PCA), MPND (Affinity Capture-Western), MPND (Proximity Label-MS), MPND (Proximity Label-MS), MPND (Proximity Label-MS), MPND (Proximity Label-MS), MPND (Two-hybrid), MPND (Affinity Capture-MS), MPND (Affinity Capture-MS), MPND (Affinity Capture-MS), MPND (Affinity Capture-MS), SNAI1 (Affinity Capture-Western), MPND (Proximity Label-MS), MPND (Affinity Capture-MS), MPND (Affinity Capture-MS)

ESM2 similar proteins: A3KP59, A5PK74, A6QQJ8, D3YY23, D3ZU57, E2RDP2, O75064, O95382, O95398, P0C5W1, P0C7A1, P16386, P52824, P54310, Q0P5G1, Q15477, Q1JPD6, Q1L5Z9, Q3T1I9, Q3TV65, Q3U1Y4, Q562E7, Q5ZMM1, Q684M2, Q68J42, Q6NZR5, Q766D5, Q76MJ5, Q80TE0, Q86TL0, Q8BGV9, Q8BIW9, Q8BMZ5, Q8BX80, Q8C052, Q8IV53, Q8K1S6, Q8N594, Q8NFI3, Q8R5G7

Diamond homologs: A0A8M3B525, A5PJP6, B0KWU8, B2RYM5, B5X8M4, E2AXC7, O35864, P46736, P46737, Q3TV65, Q4VA72, Q5R9L6, Q66GV6, Q6GLM9, Q6P635, Q6PC30, Q7M757, Q8H936, Q8N594, Q92905, Q9LT08, A6ZXB7, B3LH96, O94454, P91001, Q12468, Q4IJM4, Q4P804, Q6BMQ3, Q6C703, Q7RXX8, Q9FVU9, Q8LAZ7, Q54PF3, A0JMR6, B6MUN4, D4GTS4, P97496, Q08CH3, Q54Z40

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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.

GO biological processes:

GO term	Partners	Fold	FDR
adult locomotory behavior	5	62.7×	6e-06
learning	5	58.5×	6e-06
negative regulation of neuron apoptotic process	5	23.1×	2e-04
positive regulation of apoptotic process	5	11.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2043 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4345739:CTGCA:C	acceptor_loss	1.0000
19:4345740:TGCA:T	acceptor_loss	1.0000
19:4345741:GCAGG:G	acceptor_loss	1.0000
19:4345743:A:AG	acceptor_gain	1.0000
19:4345743:A:AT	acceptor_loss	1.0000
19:4345743:AG:A	acceptor_gain	1.0000
19:4345743:AGG:A	acceptor_gain	1.0000
19:4345744:G:GG	acceptor_gain	1.0000
19:4345744:GG:G	acceptor_gain	1.0000
19:4345744:GGG:G	acceptor_gain	1.0000
19:4345982:GTAC:G	donor_loss	1.0000
19:4345983:T:A	donor_loss	1.0000
19:4352896:GA:G	acceptor_gain	1.0000
19:4353001:G:GT	donor_gain	1.0000
19:4354041:CCA:C	acceptor_loss	1.0000
19:4354042:CA:C	acceptor_loss	1.0000
19:4354043:A:AG	acceptor_gain	1.0000
19:4354043:A:AT	acceptor_loss	1.0000
19:4354043:AGAG:A	acceptor_gain	1.0000
19:4354044:G:GT	acceptor_gain	1.0000
19:4354044:GA:G	acceptor_gain	1.0000
19:4354044:GAGG:G	acceptor_gain	1.0000
19:4354044:GAGGC:G	acceptor_gain	1.0000
19:4354126:CCAG:C	donor_loss	1.0000
19:4354127:CAGG:C	donor_loss	1.0000
19:4354129:GGTCA:G	donor_loss	1.0000
19:4354130:G:GA	donor_loss	1.0000
19:4354321:CAGGA:C	acceptor_loss	1.0000
19:4354322:AGGAA:A	acceptor_loss	1.0000
19:4355020:GA:G	donor_gain	1.0000

AlphaMissense

3261 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4345754:T:C	F102L	1.000
19:4345755:T:C	F102S	1.000
19:4345756:C:A	F102L	1.000
19:4345756:C:G	F102L	1.000
19:4345785:T:A	I112N	1.000
19:4345785:T:C	I112T	1.000
19:4345811:T:C	F121L	1.000
19:4345813:C:A	F121L	1.000
19:4345813:C:G	F121L	1.000
19:4345821:C:A	P124H	1.000
19:4345829:T:A	W127R	1.000
19:4345829:T:C	W127R	1.000
19:4345830:G:C	W127S	1.000
19:4345831:G:C	W127C	1.000
19:4345831:G:T	W127C	1.000
19:4345833:C:A	A128D	1.000
19:4345842:G:A	C131Y	1.000
19:4345843:C:G	C131W	1.000
19:4345844:A:G	K132E	1.000
19:4345846:G:C	K132N	1.000
19:4345846:G:T	K132N	1.000
19:4345881:G:A	G144D	1.000
19:4345883:T:A	W145R	1.000
19:4345883:T:C	W145R	1.000
19:4345885:G:C	W145C	1.000
19:4345885:G:T	W145C	1.000
19:4345893:T:A	V148D	1.000
19:4345927:G:C	K159N	1.000
19:4345927:G:T	K159N	1.000
19:4343978:T:C	L93P	0.999

dbSNP variants (sampled 300 via entrez): RS1000016607 (19:4347490 C>T), RS1000088517 (19:4347328 C>T), RS1000299437 (19:4342271 G>C), RS1000474617 (19:4347639 G>A), RS1000849681 (19:4355885 C>T), RS1001069301 (19:4357176 T>C,G), RS1001087623 (19:4355590 C>T), RS1001200536 (19:4357114 G>A,T), RS1001430594 (19:4360200 C>G,T), RS1001436868 (19:4356911 A>C,G), RS1001558586 (19:4359327 C>A), RS1001742340 (19:4348519 A>C,G,T), RS1001794186 (19:4359492 G>A), RS1001905463 (19:4344093 G>A), RS1001944905 (19:4344250 A>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010042_36	Asthma	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
beta-lapachone	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
Atrazine	decreases expression	1
Methapyrilene	decreases methylation	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Genistein	increases expression	1
Acrylamide	decreases expression	1
Vitamin K 3	affects expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1XF	Abcam HeLa MPND KO	Cancer cell line	Female
CVCL_SY83	HAP1 MPND (-) 1	Cancer cell line	Male
CVCL_SY84	HAP1 MPND (-) 2	Cancer cell line	Male
CVCL_XQ60	HAP1 MPND (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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