MPPED1

Summary

MPPED1 (metallophosphoesterase domain containing 1, HGNC:1306) is a protein-coding gene on chromosome 22q13.2, encoding Metallophosphoesterase domain-containing protein 1 (O15442). May have metallophosphoesterase activity (in vitro).

Predicted to enable hydrolase activity.

Source: NCBI Gene 758 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_001044370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1306
Approved symbol	MPPED1
Name	metallophosphoesterase domain containing 1
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	239AB, FAM1A
Ensembl gene	ENSG00000186732
Ensembl biotype	protein_coding
OMIM	602112
Entrez	758

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000334209, ENST00000417669, ENST00000443721, ENST00000447567, ENST00000465861, ENST00000480239, ENST00000896700, ENST00000896701

RefSeq mRNA: 2 — MANE Select: NM_001044370 NM_001044370, NM_001362786

CCDS: CCDS46723

Canonical transcript exons

ENST00000443721 — 7 exons

Exon	Start	End
ENSE00001647155	43412014	43412158
ENSE00003889385	43502644	43502757
ENSE00003889814	43474736	43474961
ENSE00003891915	43435034	43435215
ENSE00003893618	43505498	43507848
ENSE00003894908	43498235	43498350
ENSE00003895184	43424908	43425209

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 99.16.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.4222 / max 731.9634, expressed in 138 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192609	2.0524	94
192607	0.6358	62
192606	0.1705	58
192613	0.1373	41
192611	0.1305	46
192605	0.0835	41
192610	0.0791	25
209493	0.0480	15
192612	0.0353	18
192608	0.0296	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.16	gold quality
ganglionic eminence	UBERON:0004023	92.24	gold quality
prefrontal cortex	UBERON:0000451	91.71	gold quality
right frontal lobe	UBERON:0002810	90.93	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.88	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.82	gold quality
middle temporal gyrus	UBERON:0002771	90.22	gold quality
cingulate cortex	UBERON:0003027	90.08	gold quality
anterior cingulate cortex	UBERON:0009835	89.83	gold quality
neocortex	UBERON:0001950	89.46	gold quality
frontal cortex	UBERON:0001870	89.34	gold quality
endothelial cell	CL:0000115	88.49	gold quality
primary visual cortex	UBERON:0002436	87.81	gold quality
cerebral cortex	UBERON:0000956	87.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.34	gold quality
buccal mucosa cell	CL:0002336	85.88	silver quality
occipital lobe	UBERON:0002021	85.76	gold quality
superior frontal gyrus	UBERON:0002661	84.65	gold quality
right lobe of liver	UBERON:0001114	84.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.39	gold quality
postcentral gyrus	UBERON:0002581	81.49	gold quality
parietal lobe	UBERON:0001872	81.45	gold quality
telencephalon	UBERON:0001893	80.72	gold quality
amygdala	UBERON:0001876	80.47	gold quality
Ammon’s horn	UBERON:0001954	79.91	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.89	gold quality
embryo	UBERON:0000922	79.66	gold quality
temporal lobe	UBERON:0001871	79.13	gold quality
forebrain	UBERON:0001890	77.74	gold quality
tongue squamous epithelium	UBERON:0006919	77.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting MPPED1, 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-4673	100.00	66.64	1490
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-486-3P	99.51	66.82	1901

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	mpped1	ENSDARG00000088181
mus_musculus	Mpped1	ENSMUSG00000041708
rattus_norvegicus	Mpped1	ENSRNOG00000010834
drosophila_melanogaster	CG16717	FBGN0036028
caenorhabditis_elegans		WBGENE00011579
caenorhabditis_elegans		WBGENE00016101
caenorhabditis_elegans		WBGENE00019479

Paralogs (1): MPPED2 (ENSG00000066382)

Protein

Protein identifiers

Metallophosphoesterase domain-containing protein 1 — O15442 (reviewed: O15442)

Alternative names: Adult brain protein 239

All UniProt accessions (3): O15442, B1AH62, B1AH63

UniProt curated annotations — full annotation on UniProt →

Function. May have metallophosphoesterase activity (in vitro).

Tissue specificity. Expressed predominantly in adult brain.

Similarity. Belongs to the UPF0046 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15442-1	1	yes
O15442-2	2

RefSeq proteins (2): NP_001037835, NP_001349715 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004843	Calcineurin-like_PHP	Domain
IPR024201	Calcineurin-like_Pesterase	Family
IPR029052	Metallo-depent_PP-like	Homologous_superfamily
IPR051693	UPF0046_metallophosphoest	Family

Pfam: PF00149

UniProt features (2 total): chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15442-F1	88.56	0.77

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): MODULE_45, MODULE_88, chr22q13, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, MODULE_55, BLALOCK_ALZHEIMERS_DISEASE_DN, GOMF_CYCLIC_NUCLEOTIDE_PHOSPHODIESTERASE_ACTIVITY, GOMF_PHOSPHORIC_DIESTER_HYDROLASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, MIKKELSEN_IPS_WITH_HCP_H3K27ME3, MIKKELSEN_ES_HCP_WITH_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, MODULE_212

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (2): hydrolase activity (GO:0016787), molecular_function (GO:0003674)

GO Cellular Component (1): cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	1

Protein interactions and networks

STRING

1184 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPPED1	CXorf49C	A0A1B0GWI6	513
MPPED1	TTC27	Q6P3X3	429
MPPED1	AMZ1	Q400G9	417
MPPED1	FIBCD1	Q8N539	398
MPPED1	RSPRY1	Q96DX4	377
MPPED1	CCDC106	Q9BWC9	371
MPPED1	NUDT13	Q86X67	369
MPPED1	A0A2U3TZT1	A0A2U3TZT1	348
MPPED1	TPRA1	Q86W33	348
MPPED1	SULT4A1	Q9BR01	342
MPPED1	TBATA	Q96M53	341
MPPED1	FIZ1	Q96SL8	329
MPPED1	MOBP	Q13875	328
MPPED1	FYB2	Q5VWT5	321
MPPED1	PKP4	Q99569	320

IntAct

10 interactions, top by confidence:

A	B	Type	Score
MPPED1	TXNDC9	psi-mi:“MI:0914”(association)	0.640
MPPED1	CLUH	psi-mi:“MI:0914”(association)	0.640
MPPED1	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
TK1	MPPED1	psi-mi:“MI:0915”(physical association)	0.370
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
MPPED1	DISC1	psi-mi:“MI:0915”(physical association)	0.000
DISC1	MPPED1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (74): CIAO1 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), PHKA1 (Affinity Capture-MS), PHKA2 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), MMS19 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F1 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), CLUH (Affinity Capture-MS), PHKB (Affinity Capture-MS), UCKL1 (Affinity Capture-MS), NARF (Affinity Capture-MS), TXNDC9 (Affinity Capture-MS), MPPED2 (Affinity Capture-MS)

ESM2 similar proteins: A2VCW9, A4IG42, A7YY53, O15442, O54820, O97860, P06760, P09889, P12265, P13686, P17812, P29288, P70698, Q05117, Q0IHA5, Q10RB4, Q1L8D2, Q28FE0, Q29LW1, Q3LIE5, Q3ZC91, Q58DC0, Q5M886, Q5RCR9, Q5RET5, Q5U3W0, Q641Z7, Q66H71, Q66JJ3, Q6ING7, Q6NTR1, Q6ZJJ0, Q7T0Q0, Q7T291, Q811A3, Q84LR6, Q8BFS6, Q8BXJ9, Q8H5F8, Q91ZG2

Diamond homologs: B1WBP0, O15442, Q15777, Q18161, Q21268, Q22306, Q5B5P1, Q5REB1, Q91ZG2, Q9CZJ0, A1D144, A5ABH4, B0XPA2, B8N5T6, Q0C7K7, Q2U5P7, Q2UDJ8, Q4WR79, Q5AZ85

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2121 predictions. Top by Δscore:

Variant	Effect	Δscore
22:43425207:GAT:G	donor_gain	1.0000
22:43435214:GG:G	donor_gain	1.0000
22:43435215:GG:G	donor_gain	1.0000
22:43435215:GGTA:G	donor_loss	1.0000
22:43435216:G:GA	donor_loss	1.0000
22:43435216:G:GG	donor_gain	1.0000
22:43435217:T:G	donor_loss	1.0000
22:43474960:TGG:T	donor_loss	1.0000
22:43474961:GGT:G	donor_loss	1.0000
22:43474963:T:G	donor_loss	1.0000
22:43498349:GG:G	donor_gain	1.0000
22:43498350:GG:G	donor_gain	1.0000
22:43498351:GTAA:G	donor_loss	1.0000
22:43498352:T:TC	donor_loss	1.0000
22:43502762:G:GG	donor_gain	1.0000
22:43425210:G:GG	donor_gain	0.9900
22:43435029:TGCAG:T	acceptor_loss	0.9900
22:43435031:CA:C	acceptor_loss	0.9900
22:43435032:A:AG	acceptor_gain	0.9900
22:43435032:AG:A	acceptor_gain	0.9900
22:43435032:AGGGT:A	acceptor_gain	0.9900
22:43435033:G:GA	acceptor_gain	0.9900
22:43435033:GG:G	acceptor_gain	0.9900
22:43435033:GGGT:G	acceptor_gain	0.9900
22:43435033:GGGTG:G	acceptor_gain	0.9900
22:43435211:GCTGG:G	donor_gain	0.9900
22:43451579:G:T	donor_gain	0.9900
22:43474921:G:GT	donor_gain	0.9900
22:43474960:TG:T	donor_gain	0.9900
22:43474961:GG:G	donor_gain	0.9900

AlphaMissense

2142 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:43435087:T:A	V93D	1.000
22:43435096:C:T	S96F	1.000
22:43435158:G:T	G117W	1.000
22:43435159:G:A	G117E	1.000
22:43435162:A:T	D118V	1.000
22:43435176:G:A	G123R	1.000
22:43435176:G:C	G123R	1.000
22:43435176:G:T	G123W	1.000
22:43435177:G:A	G123E	1.000
22:43474772:G:T	G148V	1.000
22:43474776:C:A	N149K	1.000
22:43474776:C:G	N149K	1.000
22:43474777:C:G	H150D	1.000
22:43498260:T:C	F220L	1.000
22:43498262:C:A	F220L	1.000
22:43498262:C:G	F220L	1.000
22:43498296:T:A	W232R	1.000
22:43498296:T:C	W232R	1.000
22:43502652:G:C	D253H	1.000
22:43502653:A:T	D253V	1.000
22:43502682:G:C	G263R	1.000
22:43502695:T:C	L267P	1.000
22:43505538:T:A	N301K	1.000
22:43505538:T:G	N301K	1.000
22:43425157:T:C	F58L	0.999
22:43425159:C:A	F58L	0.999
22:43425159:C:G	F58L	0.999
22:43435080:C:A	R91S	0.999
22:43435081:G:C	R91P	0.999
22:43435084:T:C	F92S	0.999

dbSNP variants (sampled 300 via entrez): RS1000024228 (22:43420504 A>C,G), RS1000030843 (22:43490616 A>T), RS1000040199 (22:43483312 C>G,T), RS1000044353 (22:43470636 A>G), RS1000051170 (22:43412413 C>G), RS1000054780 (22:43436526 C>T), RS1000092842 (22:43460874 T>G), RS1000128074 (22:43436339 CA>C), RS1000164956 (22:43503729 G>A,T), RS1000165301 (22:43411325 G>A), RS1000195565 (22:43490867 C>T), RS1000199022 (22:43488093 G>A,C,T), RS1000225029 (22:43447801 A>T), RS1000260147 (22:43483040 C>G), RS1000271312 (22:43437376 G>A)

Disease associations

OMIM: gene MIM:602112 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004862_109	Itch intensity from mosquito bite adjusted by bite size	2.000000e-07
GCST012034_12	Sleep (1/2-day periodicity)	1.000000e-08
GCST012490_107	Femur bone mineral density x serum urate levels interaction	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
pirinixic acid	affects binding, decreases expression, increases activity	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
tetrachlorodian	increases expression	1
Vehicle Emissions	decreases methylation	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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