MB21D2

Summary

MB21D2 (Mab-21 domain containing 2, HGNC:30438) is a protein-coding gene on chromosome 3q29, encoding Nucleotidyltransferase MB21D2 (Q8IYB1). Probable nucleotidyltransferase that catalyzes the formation of cyclic dinucleotide second messenger in response to some unknown stimulus.

Enables cadherin binding activity.

Source: NCBI Gene 151963 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 61 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 4 cancer types
• MANE Select transcript: NM_178496

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30438
Approved symbol	MB21D2
Name	Mab-21 domain containing 2
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	D2A
Ensembl gene	ENSG00000180611
Ensembl biotype	protein_coding
OMIM	620914
Entrez	151963

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000392452

RefSeq mRNA: 1 — MANE Select: NM_178496 NM_178496

CCDS: CCDS3302

Canonical transcript exons

ENST00000392452 — 2 exons

Exon	Start	End
ENSE00001326154	192917630	192917856
ENSE00001863084	192796815	192799650

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 97.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8235 / max 137.0440, expressed in 1614 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46145	6.8772	1542
46147	0.6374	346
46149	0.5473	303
46148	0.4165	221
46146	0.3450	177

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.64	gold quality
endothelial cell	CL:0000115	93.41	gold quality
oocyte	CL:0000023	91.51	gold quality
vena cava	UBERON:0004087	91.42	gold quality
middle temporal gyrus	UBERON:0002771	89.55	gold quality
cortical plate	UBERON:0005343	88.76	gold quality
pericardium	UBERON:0002407	88.16	gold quality
saphenous vein	UBERON:0007318	88.09	gold quality
placenta	UBERON:0001987	87.65	gold quality
buccal mucosa cell	CL:0002336	87.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.84	gold quality
ileal mucosa	UBERON:0000331	85.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.37	gold quality
oviduct epithelium	UBERON:0004804	85.25	gold quality
upper arm skin	UBERON:0004263	85.19	silver quality
lower lobe of lung	UBERON:0008949	83.20	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.18	gold quality
jejunal mucosa	UBERON:0000399	83.01	gold quality
epithelial cell of pancreas	CL:0000083	82.61	silver quality
cartilage tissue	UBERON:0002418	82.46	gold quality
epithelium of mammary gland	UBERON:0003244	82.32	gold quality
mammary duct	UBERON:0001765	82.21	gold quality
trachea	UBERON:0003126	82.21	gold quality
pons	UBERON:0000988	82.03	gold quality
trigeminal ganglion	UBERON:0001675	81.90	gold quality
nipple	UBERON:0002030	81.76	gold quality
parietal pleura	UBERON:0002400	81.52	gold quality
duodenum	UBERON:0002114	81.49	gold quality
sperm	CL:0000019	81.34	gold quality
tibia	UBERON:0000979	81.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

159 targeting MB21D2, 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-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 1)

• Overexpression of wild type or a Q311E mutant MB21D2 promotes a pro-oncogenic phenotype in HNSCC. (PMID:32979859)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	MB21D2	ENSDARG00000077316
danio_rerio	mb21d2	ENSDARG00000077690
mus_musculus	Mb21d2	ENSMUSG00000051065
rattus_norvegicus	Mb21d2	ENSRNOG00000024040
drosophila_melanogaster	CG15865	FBGN0015336

Paralogs (9): ITPRIP (ENSG00000148841), CGAS (ENSG00000164430), MAB21L4 (ENSG00000172478), MAB21L3 (ENSG00000173212), MAB21L1 (ENSG00000180660), TMEM102 (ENSG00000181284), MAB21L2 (ENSG00000181541), ITPRIPL1 (ENSG00000198885), ITPRIPL2 (ENSG00000205730)

Protein

Protein identifiers

Nucleotidyltransferase MB21D2 — Q8IYB1 (reviewed: Q8IYB1)

Alternative names: Mab-21 domain-containing protein 2

All UniProt accessions (1): Q8IYB1

UniProt curated annotations — full annotation on UniProt →

Function. Probable nucleotidyltransferase that catalyzes the formation of cyclic dinucleotide second messenger in response to some unknown stimulus.

Similarity. Belongs to the mab-21 family.

RefSeq proteins (1): NP_848591* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024810	MAB21L/cGLR	Family
IPR046903	Mab-21-like_nuc_Trfase	Domain
IPR046906	Mab-21_HhH/H2TH-like	Domain

Pfam: PF03281, PF20266

UniProt features (45 total): helix 18, strand 15, turn 4, modified residue 4, chain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7LT1	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYB1-F1	83.98	0.62

Functional residue map

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

Post-translational modifications (4): 435, 436, 439, 442

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, SHEPARD_BMYB_MORPHOLINO_UP, GOZGIT_ESR1_TARGETS_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_DN, ENGELMANN_CANCER_PROGENITORS_UP, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, AACTTT_UNKNOWN, CTGYNNCTYTAA_UNKNOWN, CTTTGTA_MIR524, TTTGCAC_MIR19A_MIR19B, ZHAN_MULTIPLE_MYELOMA_CD2_DN, GOMF_CELL_ADHESION_MOLECULE_BINDING, GOMF_CADHERIN_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS

GO Biological Process (0):

GO Molecular Function (5): nucleotidyltransferase activity (GO:0016779), protein-containing complex binding (GO:0044877), cadherin binding (GO:0045296), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
transferase activity, transferring phosphorus-containing groups	1
cell adhesion molecule binding	1
catalytic activity	1

Protein interactions and networks

STRING

410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MB21D2	MAB21L3	Q8N8X9	602
MB21D2	TOX4	O94842	548
MB21D2	C3orf70	A6NLC5	471
MB21D2	ITPRIPL2	Q3MIP1	462
MB21D2	MROH2B	Q7Z745	451
MB21D2	TBC1D12	O60347	444
MB21D2	CDH17	Q12864	424
MB21D2	NOVA1	P51513	421
MB21D2	OR52J3	Q8NH60	419
MB21D2	ITPRIPL1	Q6GPH6	417
MB21D2	CDH1	P12830	410
MB21D2	CCDC148	Q8NFR7	403
MB21D2	LMBR1	Q8WVP7	401
MB21D2	KANSL1L	A0AUZ9	397
MB21D2	ITPRIP	Q8IWB1	387

IntAct

107 interactions, top by confidence:

A	B	Type	Score
RAB3IP	TRAPPC3	psi-mi:“MI:0914”(association)	0.700
EVI5	MB21D2	psi-mi:“MI:0915”(physical association)	0.670
MB21D2	RAB3IP	psi-mi:“MI:0915”(physical association)	0.560
REL	MB21D2	psi-mi:“MI:0915”(physical association)	0.560
MB21D2	SLC12A4	psi-mi:“MI:0915”(physical association)	0.560
CIR1	MB21D2	psi-mi:“MI:0915”(physical association)	0.560
	MB21D2	psi-mi:“MI:0915”(physical association)	0.560
MB21D2	CBX8	psi-mi:“MI:0915”(physical association)	0.560
MORN3	MB21D2	psi-mi:“MI:0915”(physical association)	0.560
ARHGEF5	MB21D2	psi-mi:“MI:0915”(physical association)	0.560
BYSL	MB21D2	psi-mi:“MI:0915”(physical association)	0.560
DTNB	MB21D2	psi-mi:“MI:0915”(physical association)	0.560
SPRY1	MB21D2	psi-mi:“MI:0915”(physical association)	0.560
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
CAVIN1	ZZEF1	psi-mi:“MI:0914”(association)	0.530
KCNJ6	MB21D2	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
CC2D2A	OFD1	psi-mi:“MI:2364”(proximity)	0.420
AHI1	OFD1	psi-mi:“MI:2364”(proximity)	0.420
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
KCNJ6	HSDL1	psi-mi:“MI:0914”(association)	0.350
	DNAJB6	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350
EVI5	RGPD8	psi-mi:“MI:0914”(association)	0.350

BioGRID (119): MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Proximity Label-MS), MB21D2 (Affinity Capture-MS), MB21D2 (Affinity Capture-MS)

ESM2 similar proteins: A2AKB9, A4IFQ0, O42224, Q08BT5, Q13769, Q148V7, Q1A730, Q1RMS8, Q1RMZ1, Q2KHT6, Q3T0J1, Q3UGM2, Q4R372, Q4R6Y6, Q5BK68, Q5E9M5, Q5RAQ5, Q5T9G4, Q62784, Q641X7, Q68FX7, Q6IC98, Q6P6Y1, Q6ZPY2, Q6ZWH5, Q7Z6M2, Q8BKT7, Q8BXK4, Q8CB44, Q8CHQ0, Q8IYB1, Q8NFG4, Q8TCJ0, Q8VE08, Q8VE33, Q91W96, Q91Z62, Q92966, Q93008, Q969P5

Diamond homologs: Q1LZD1, Q3UPR7, Q8IYB1, Q8N9M5, Q8C525

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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
COPII-mediated vesicle transport	7	18.4×	1e-05
RAB GEFs exchange GTP for GDP on RABs	8	16.0×	1e-05
Anchoring of the basal body to the plasma membrane	8	14.6×	1e-05
Constitutive Signaling by Aberrant PI3K in Cancer	7	14.3×	4e-05
RHOB GTPase cycle	5	12.4×	3e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	7	10.9×	2e-04
PIP3 activates AKT signaling	9	9.7×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle tethering	6	78.3×	3e-08
motile cilium assembly	5	38.2×	3e-05
non-motile cilium assembly	6	22.9×	4e-05
cell surface receptor protein tyrosine kinase signaling pathway	6	13.7×	5e-04
endoplasmic reticulum to Golgi vesicle-mediated transport	7	12.5×	2e-04
positive regulation of neuron projection development	6	10.8×	1e-03
cilium assembly	10	9.7×	2e-05
protein autophosphorylation	5	9.6×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 4 cancer types — HNSC, LIPO, LUSC, UTUC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1172 predictions. Top by Δscore:

Variant	Effect	Δscore
3:192799646:CATTC:C	acceptor_gain	1.0000
3:192799647:ATTC:A	acceptor_gain	1.0000
3:192799648:TTC:T	acceptor_gain	1.0000
3:192799649:TC:T	acceptor_gain	1.0000
3:192799650:CC:C	acceptor_gain	1.0000
3:192799651:C:CA	acceptor_loss	1.0000
3:192799651:C:CC	acceptor_gain	1.0000
3:192799657:A:AC	acceptor_gain	1.0000
3:192799657:A:C	acceptor_gain	1.0000
3:192917625:CTTA:C	donor_loss	1.0000
3:192917626:TTA:T	donor_loss	1.0000
3:192917627:TACCC:T	donor_loss	1.0000
3:192917628:A:AC	donor_gain	1.0000
3:192917628:AC:A	donor_gain	1.0000
3:192917629:C:CC	donor_gain	1.0000
3:192917629:CC:C	donor_gain	1.0000
3:192917629:CCCAG:C	donor_gain	1.0000
3:192917650:T:TA	donor_gain	1.0000
3:192799651:C:T	acceptor_gain	0.9900
3:192799652:T:A	acceptor_loss	0.9900
3:192917628:ACC:A	donor_gain	0.9900
3:192917629:CCC:C	donor_gain	0.9900
3:192917633:G:C	donor_gain	0.9900
3:192917623:T:TA	donor_gain	0.9800
3:192917629:CCCA:C	donor_gain	0.9800
3:192816706:A:T	acceptor_gain	0.9600
3:192886840:G:A	donor_gain	0.9600
3:192799647:ATTCC:A	acceptor_gain	0.9500
3:192799648:TTCC:T	acceptor_gain	0.9500
3:192799649:TCCT:T	acceptor_gain	0.9500

AlphaMissense

3266 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:192798392:A:C	F490L	1.000
3:192798392:A:T	F490L	1.000
3:192798393:A:C	F490C	1.000
3:192798393:A:G	F490S	1.000
3:192798394:A:G	F490L	1.000
3:192798402:T:A	D487V	1.000
3:192798403:C:A	D487Y	1.000
3:192798403:C:G	D487H	1.000
3:192798405:A:C	I486S	1.000
3:192798405:A:T	I486N	1.000
3:192798407:T:A	R485S	1.000
3:192798407:T:G	R485S	1.000
3:192798408:C:G	R485T	1.000
3:192798409:T:C	R485G	1.000
3:192798410:G:C	F484L	1.000
3:192798410:G:T	F484L	1.000
3:192798411:A:C	F484C	1.000
3:192798411:A:G	F484S	1.000
3:192798412:A:G	F484L	1.000
3:192798443:A:C	F473L	1.000
3:192798443:A:T	F473L	1.000
3:192798444:A:C	F473C	1.000
3:192798444:A:G	F473S	1.000
3:192798445:A:G	F473L	1.000
3:192798447:A:T	V472D	1.000
3:192798450:G:A	S471F	1.000
3:192798450:G:T	S471Y	1.000
3:192798451:A:G	S471P	1.000
3:192798453:A:C	I470S	1.000
3:192798453:A:G	I470T	1.000

dbSNP variants (sampled 300 via entrez): RS1000019143 (3:192815805 A>G), RS1000019995 (3:192891191 A>T), RS1000026258 (3:192855697 A>G), RS1000029031 (3:192907407 T>C), RS1000038740 (3:192916335 G>C), RS1000069782 (3:192815571 A>G), RS1000085833 (3:192810333 A>C), RS1000101036 (3:192821148 C>T), RS1000117377 (3:192798266 A>G), RS1000133951 (3:192898469 G>A), RS1000136113 (3:192816569 G>C), RS1000154937 (3:192833300 T>A,C), RS1000167857 (3:192856972 C>A,G), RS1000176146 (3:192821787 T>C,G), RS1000225586 (3:192876416 C>G)

Disease associations

OMIM: gene MIM:620914 | 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
GCST005025_32	Anti-saccade response	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006874	antisaccade response measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression	4
Benzo(a)pyrene	decreases methylation, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
Air Pollutants	affects methylation, increases abundance, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
urushiol	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Rosiglitazone	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Pioglitazone	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	increases methylation	1
Troglitazone	affects cotreatment, decreases expression, decreases reaction	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression, affects cotreatment	1
Coumestrol	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Methyl Methanesulfonate	decreases expression	1
Nitrogen Oxides	affects methylation, increases abundance	1

Clinical trials (associated diseases)

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