MANEAL

Summary

MANEAL (mannosidase endo-alpha like, HGNC:26452) is a protein-coding gene on chromosome 1p34.3, encoding Glycoprotein endo-alpha-1,2-mannosidase-like protein (Q5VSG8).

Predicted to enable alpha-mannosidase activity. Predicted to be located in Golgi membrane.

Source: NCBI Gene 149175 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 66 total — 1 likely-pathogenic
• MANE Select transcript: NM_001113482

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26452
Approved symbol	MANEAL
Name	mannosidase endo-alpha like
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31434
Ensembl gene	ENSG00000185090
Ensembl biotype	protein_coding
OMIM	620919
Entrez	149175

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000329006, ENST00000373045, ENST00000397631, ENST00000525897, ENST00000532512, ENST00000867387, ENST00000951301

RefSeq mRNA: 3 — MANE Select: NM_001113482 NM_001031740, NM_001113482, NM_152496

CCDS: CCDS426, CCDS44110, CCDS44111

Canonical transcript exons

ENST00000373045 — 4 exons

Exon	Start	End
ENSE00001377582	37796744	37796820
ENSE00001881202	37799567	37801133
ENSE00002164884	37793847	37794732
ENSE00003503859	37795737	37795846

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 91.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3299 / max 122.4696, expressed in 1184 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2220	4.1393	977
2218	3.3918	840
2219	0.7647	353
2221	0.0341	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	91.25	gold quality
ganglionic eminence	UBERON:0004023	90.14	gold quality
islet of Langerhans	UBERON:0000006	89.66	gold quality
prefrontal cortex	UBERON:0000451	88.16	gold quality
hypothalamus	UBERON:0001898	86.39	gold quality
adenohypophysis	UBERON:0002196	85.22	gold quality
pituitary gland	UBERON:0000007	84.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.71	gold quality
right frontal lobe	UBERON:0002810	84.69	gold quality
anterior cingulate cortex	UBERON:0009835	84.43	gold quality
frontal cortex	UBERON:0001870	84.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.05	gold quality
neocortex	UBERON:0001950	83.85	gold quality
nucleus accumbens	UBERON:0001882	83.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.52	gold quality
amygdala	UBERON:0001876	82.23	gold quality
cerebral cortex	UBERON:0000956	81.90	gold quality
forebrain	UBERON:0001890	81.77	gold quality
putamen	UBERON:0001874	81.47	gold quality
brain	UBERON:0000955	81.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.28	gold quality
caudate nucleus	UBERON:0001873	81.20	gold quality
cerebellar hemisphere	UBERON:0002245	80.82	gold quality
cerebellar cortex	UBERON:0002129	80.80	gold quality
endothelial cell	CL:0000115	80.56	silver quality
cerebellum	UBERON:0002037	80.32	gold quality
pancreas	UBERON:0001264	80.26	gold quality
ileal mucosa	UBERON:0000331	80.10	gold quality
Ammon’s horn	UBERON:0001954	79.18	gold quality
dorsal root ganglion	UBERON:0000044	79.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting MANEAL, 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-4692	100.00	67.32	2066
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-3125	99.14	68.49	2269

Literature-anchored findings (GeneRIF, showing 1)

• Loss-of-function variant in MANEAL, coexisting with OSTM1 mutation was identified in a patient with neurological disorder with brain iron accumulation. (PMID:28612835)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	maneal	ENSDARG00000056450
mus_musculus	Maneal	ENSMUSG00000042763
rattus_norvegicus	Maneal	ENSRNOG00000025349
drosophila_melanogaster	CG14015	FBGN0031716

Paralogs (1): MANEA (ENSG00000172469)

Protein

Protein identifiers

Glycoprotein endo-alpha-1,2-mannosidase-like protein — Q5VSG8 (reviewed: Q5VSG8)

All UniProt accessions (3): Q5VSG8, E9PMU5, H0YCZ3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Golgi apparatus membrane.

Similarity. Belongs to the glycosyl hydrolase 99 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5VSG8-1	1	yes
Q5VSG8-2	2
Q5VSG8-3	3

RefSeq proteins (3): NP_001026910, NP_001106954, NP_689709 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026071	Glyco_Hydrolase_99	Family

Pfam: PF16317

UniProt features (11 total): splice variant 4, topological domain 2, compositionally biased region 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VSG8-F1	87.80	0.77

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 83 (showing top): ACTACCT_MIR196A_MIR196B, MYOGENIN_Q6, SP3_Q3, ATACCTC_MIR202, AACWWCAANK_UNKNOWN, SRF_C, BILD_E2F3_ONCOGENIC_SIGNATURE, GGARNTKYCCA_UNKNOWN, chr1p34, TGACATY_UNKNOWN, MYOD_Q6, NKX22_01, DODD_NASOPHARYNGEAL_CARCINOMA_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, E12_Q6

GO Biological Process (0):

GO Molecular Function (3): alpha-mannosidase activity (GO:0004559), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (3): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mannosidase activity	1
catalytic activity	1
hydrolase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2021 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MANEAL	FAM124B	Q9H5Z6	448
MANEAL	KIAA0408	Q6ZU52	434
MANEAL	PDIK1L	Q8N165	434
MANEAL	DPY19L3	Q6ZPD9	418
MANEAL	TMEM161A	Q9NX61	414
MANEAL	AMZ1	Q400G9	413
MANEAL	EPHA5	P54756	406
MANEAL	C1orf122	Q6ZSJ8	394
MANEAL	PRPSAP1	Q14558	389
MANEAL	EXTL1	Q92935	388
MANEAL	ZXDB	P98169	387
MANEAL	ANKRD34A	Q69YU3	382
MANEAL	EPHA8	P29322	374
MANEAL	ADPRHL1	Q8NDY3	371
MANEAL	SF3A3	Q12874	363

IntAct

48 interactions, top by confidence:

A	B	Type	Score
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
MME	TMEM223	psi-mi:“MI:0914”(association)	0.530
ST8SIA3	KLRG2	psi-mi:“MI:0914”(association)	0.530
PLXDC2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
CSGALNACT2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
BCHE	SHTN1	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
IL17RC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
NAAA	POTEF	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
ASIC4	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
SLC39A12		psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
HTR3C	GET1	psi-mi:“MI:0914”(association)	0.350
SAAL1	QSOX1	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
ST3GAL4	NDUFA4	psi-mi:“MI:0914”(association)	0.350
PCDHB11	SDCBP	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	TOR1A	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
ADAM33	ADAM10	psi-mi:“MI:0914”(association)	0.350
TMPRSS11B	ADAM10	psi-mi:“MI:0914”(association)	0.350
IDS	COCH	psi-mi:“MI:0914”(association)	0.350

BioGRID (70): MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS), MANEAL (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3NGV2, A2VE47, D3Z2R5, F1N2K1, O95479, P56201, P58499, Q08DJ7, Q09200, Q0VCN6, Q10468, Q1JPD2, Q2TBP8, Q32KV6, Q3SZL5, Q3U2U7, Q5R5N9, Q5VSG8, Q5XI31, Q5XIA1, Q5ZJH2, Q642A7, Q6MG55, Q6NZ07, Q6P1J0, Q6P6S4, Q6PBN5, Q6PD26, Q7TMC8, Q7Z3D6, Q86S40, Q8BXQ2, Q8CFX1, Q8JHZ8, Q8N0W3, Q8NHY0, Q8QZW3, Q8R553, Q8VCM8, Q8VDL4

Diamond homologs: Q1L8D2, Q5GF25, Q5RD93, Q5SRI9, Q5VSG8, Q6DE40, Q6NXH2, Q6P1J0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metal ion SLC transporters	5	60.1×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
intracellular monoatomic cation homeostasis	5	89.2×	3e-07
zinc ion transmembrane transport	7	78.0×	5e-10
intracellular zinc ion homeostasis	6	45.9×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	60
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
976661	NM_001113482.2(MANEAL):c.446dup (p.Asp150fs)	Likely pathogenic

SpliceAI

936 predictions. Top by Δscore:

Variant	Effect	Δscore
1:37794720:G:GT	donor_gain	1.0000
1:37794729:ATCGG:A	donor_loss	1.0000
1:37794730:TCG:T	donor_gain	1.0000
1:37794730:TCGG:T	donor_loss	1.0000
1:37794732:GGT:G	donor_loss	1.0000
1:37794733:G:GG	donor_gain	1.0000
1:37794734:T:A	donor_loss	1.0000
1:37795729:C:CA	acceptor_gain	1.0000
1:37795734:CA:C	acceptor_loss	1.0000
1:37795735:A:AG	acceptor_gain	1.0000
1:37795736:G:GT	acceptor_gain	1.0000
1:37795736:GGC:G	acceptor_gain	1.0000
1:37795844:CAGGT:C	donor_loss	1.0000
1:37795846:GGT:G	donor_loss	1.0000
1:37795847:G:GC	donor_loss	1.0000
1:37795847:G:GG	donor_gain	1.0000
1:37795848:T:G	donor_loss	1.0000
1:37796736:T:TA	acceptor_gain	1.0000
1:37796738:T:TA	acceptor_gain	1.0000
1:37796739:G:A	acceptor_gain	1.0000
1:37796741:CAGG:C	acceptor_loss	1.0000
1:37796742:A:AG	acceptor_gain	1.0000
1:37796742:AGGT:A	acceptor_gain	1.0000
1:37796743:G:A	acceptor_loss	1.0000
1:37796743:G:GG	acceptor_gain	1.0000
1:37796743:GGT:G	acceptor_gain	1.0000
1:37796743:GGTG:G	acceptor_gain	1.0000
1:37796816:GACAC:G	donor_gain	1.0000
1:37796817:ACAC:A	donor_gain	1.0000
1:37796818:CAC:C	donor_gain	1.0000

AlphaMissense

2979 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:37794555:T:A	W125R	1.000
1:37794555:T:C	W125R	1.000
1:37794557:G:C	W125C	1.000
1:37794557:G:T	W125C	1.000
1:37799805:T:C	F326L	1.000
1:37799807:T:A	F326L	1.000
1:37799807:T:G	F326L	1.000
1:37799820:T:C	F331L	1.000
1:37799822:C:A	F331L	1.000
1:37799822:C:G	F331L	1.000
1:37799847:T:A	W340R	1.000
1:37799847:T:C	W340R	1.000
1:37799898:A:C	S357R	1.000
1:37799900:T:A	S357R	1.000
1:37799900:T:G	S357R	1.000
1:37799904:G:T	G359W	1.000
1:37799908:C:A	P360H	1.000
1:37799910:G:C	G361R	1.000
1:37799911:G:A	G361D	1.000
1:37799937:T:A	W370R	1.000
1:37799937:T:C	W370R	1.000
1:37799939:G:C	W370C	1.000
1:37799939:G:T	W370C	1.000
1:37799962:G:C	R378T	1.000
1:37799962:G:T	R378M	1.000
1:37799963:G:C	R378S	1.000
1:37799963:G:T	R378S	1.000
1:37800037:C:T	S403F	1.000
1:37800048:T:A	W407R	1.000
1:37800048:T:C	W407R	1.000

dbSNP variants (sampled 300 via entrez): RS1000486232 (1:37793775 G>C), RS1000991413 (1:37799087 A>T), RS1001059145 (1:37794153 C>A,T), RS1001493216 (1:37798711 C>G,T), RS1002696405 (1:37799081 A>G), RS1003756931 (1:37797270 G>A), RS1003913504 (1:37798569 AT>A,ATT), RS1005069361 (1:37796049 G>A), RS1005405381 (1:37796456 C>A,T), RS1005594619 (1:37796788 T>C,G), RS1005623506 (1:37792924 G>T), RS1005766813 (1:37800416 G>A), RS1005813776 (1:37796186 G>A), RS1006049586 (1:37801593 ACCTGTAAT>A), RS1006256381 (1:37800108 T>C)

Disease associations

OMIM: gene MIM:620919 | 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
GCST003476_2	Eyebrow thickness	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression	2
Vehicle Emissions	increases abundance, increases expression	2
Estradiol	affects binding, increases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
terbufos	decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
afimoxifene	decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Atrazine	decreases expression	1
Calcitriol	increases expression	1
Fonofos	decreases methylation	1
Estrogens	decreases reaction, increases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Parathion	decreases methylation	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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