MAB21L4

Summary

MAB21L4 (mab-21 like 4, HGNC:26216) is a protein-coding gene on chromosome 2q37.3, encoding Protein mab-21-like 4 (Q08AI8).

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 18 total — 1 pathogenic
• MANE Select transcript: NM_001085437

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26216
Approved symbol	MAB21L4
Name	mab-21 like 4
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22671
Ensembl gene	ENSG00000172478
Ensembl biotype	protein_coding
Entrez	79919

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000307486, ENST00000388934, ENST00000402775, ENST00000414499, ENST00000454476, ENST00000875446, ENST00000875447, ENST00000875448, ENST00000875449

RefSeq mRNA: 3 — MANE Select: NM_001085437 NM_001085437, NM_001282921, NM_024861

CCDS: CCDS42839, CCDS42840, CCDS63187

Canonical transcript exons

ENST00000388934 — 5 exons

Exon	Start	End
ENSE00001162289	240888292	240888648
ENSE00001162300	240890005	240890158
ENSE00001177602	240891538	240891763
ENSE00001504429	240895484	240896156
ENSE00001794003	240886048	240887162

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 99.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5274 / max 97.6619, expressed in 128 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34867	0.1838	53
34868	0.1412	43
34866	0.1066	44
34869	0.0506	20
34865	0.0453	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.04	gold quality
esophagus mucosa	UBERON:0002469	96.80	gold quality
tongue squamous epithelium	UBERON:0006919	90.95	gold quality
skin of abdomen	UBERON:0001416	90.61	gold quality
skin of leg	UBERON:0001511	90.28	gold quality
epithelium of esophagus	UBERON:0001976	89.54	gold quality
esophagus squamous epithelium	UBERON:0006920	89.14	gold quality
zone of skin	UBERON:0000014	87.74	gold quality
cervix epithelium	UBERON:0004801	86.76	silver quality
squamous epithelium	UBERON:0006914	86.29	gold quality
cervix squamous epithelium	UBERON:0006922	86.05	silver quality
oral cavity	UBERON:0000167	85.61	gold quality
upper arm skin	UBERON:0004263	85.43	silver quality
pharyngeal mucosa	UBERON:0000355	85.17	gold quality
mucosa of transverse colon	UBERON:0004991	82.34	gold quality
vagina	UBERON:0000996	81.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.59	gold quality
diaphragm	UBERON:0001103	79.17	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.88	gold quality
amniotic fluid	UBERON:0000173	78.57	gold quality
gingiva	UBERON:0001828	78.53	gold quality
right lung	UBERON:0002167	77.86	gold quality
gingival epithelium	UBERON:0001949	77.20	silver quality
upper lobe of left lung	UBERON:0008952	77.01	gold quality
upper lobe of lung	UBERON:0008948	76.55	gold quality
epithelium of nasopharynx	UBERON:0001951	76.26	silver quality
buccal mucosa cell	CL:0002336	75.24	gold quality
oviduct epithelium	UBERON:0004804	74.71	silver quality
esophagus	UBERON:0001043	73.42	gold quality
tonsil	UBERON:0002372	73.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-5061	no	3.42
E-ANND-3	no	2.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting MAB21L4, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-4773	98.35	67.30	1710

Literature-anchored findings (GeneRIF, showing 2)

• MAB21L4 regulates the TGF-beta-induced expression of target genes in epidermal keratinocytes. (PMID:34908107)
• MAB21L4 Deficiency Drives Squamous Cell Carcinoma via Activation of RET. (PMID:35705526)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mab21l4	ENSMUSG00000034159
rattus_norvegicus	Mab21l4	ENSRNOG00000023557

Paralogs (9): ITPRIP (ENSG00000148841), CGAS (ENSG00000164430), MAB21L3 (ENSG00000173212), MB21D2 (ENSG00000180611), MAB21L1 (ENSG00000180660), TMEM102 (ENSG00000181284), MAB21L2 (ENSG00000181541), ITPRIPL1 (ENSG00000198885), ITPRIPL2 (ENSG00000205730)

Protein

Protein identifiers

Protein mab-21-like 4 — Q08AI8 (reviewed: Q08AI8)

All UniProt accessions (3): C9JEK0, C9JP86, Q08AI8

Isoforms (3)

UniProt ID	Names	Canonical?
Q08AI8-1	1	yes
Q08AI8-2	2
Q08AI8-3	3

RefSeq proteins (3): NP_001078906, NP_001269850, NP_079137 (=MANE)

Domains & families (InterPro)

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

Pfam: PF20266

UniProt features (11 total): splice variant 4, sequence conflict 4, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08AI8-F1	85.07	0.54

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): DODD_NASOPHARYNGEAL_CARCINOMA_DN, CHEN_LIVER_METABOLISM_QTL_CIS, KRAS.AMP.LUNG_UP.V1_DN, NFKBIA_TARGET_GENES, SUPT16H_TARGET_GENES, TAFAZZIN_TARGET_GENES, MIR4516, SMID_BREAST_CANCER_ERBB2_UP, MIR583, GSE13485_DAY1_VS_DAY7_YF17D_VACCINE_PBMC_UP, BLANCO_MELO_BETA_INTERFERON_TREATED_BRONCHIAL_EPITHELIAL_CELLS_DN, GSE1460_INTRATHYMIC_T_PROGENITOR_VS_NAIVE_CD4_TCELL_CORD_BLOOD_DN, GSE1460_INTRATHYMIC_T_PROGENITOR_VS_THYMIC_STROMAL_CELL_UP, GSE14769_UNSTIM_VS_20MIN_LPS_BMDM_UP, chr2q37

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAB21L4	IGFL4	Q6B9Z1	478
MAB21L4	CROCC2	H7BZ55	447
MAB21L4	RTP5	Q14D33	418
MAB21L4	ANKMY1	Q9P2S6	398
MAB21L4	XKRX	Q6PP77	392
MAB21L4	ITPRIPL2	Q3MIP1	375
MAB21L4	RNPEPL1	Q9HAU8	370
MAB21L4	SPINK8	P0C7L1	368
MAB21L4	GFOD2	Q3B7J2	366
MAB21L4	MAB21L2	Q9Y586	359
MAB21L4	FAM171B	Q6P995	357
MAB21L4	THAP4	Q8WY91	357
MAB21L4	TENT5D	Q8NEK8	356
MAB21L4	TMEM102	Q8N9M5	353
MAB21L4	TENT5B	Q96A09	348
MAB21L4	ITPRIPL1	Q6GPH6	348

IntAct

10 interactions, top by confidence:

A	B	Type	Score
MAB21L4	NIPSNAP3A	psi-mi:“MI:0915”(physical association)	0.400
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
PIGT	A2ML1	psi-mi:“MI:0914”(association)	0.350
PHF11	A2ML1	psi-mi:“MI:0914”(association)	0.350
RSRP1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): NIPSNAP3A (Affinity Capture-MS), C2orf54 (Affinity Capture-MS), C2orf54 (Affinity Capture-MS), C2orf54 (Affinity Capture-MS), C2orf54 (Affinity Capture-MS), C2orf54 (Affinity Capture-MS), C2orf54 (Affinity Capture-MS), C2orf54 (Affinity Capture-MS), CACYBP (Affinity Capture-Western), CACYBP (Co-localization), C2orf54 (Affinity Capture-MS), C2orf54 (Co-fractionation)

ESM2 similar proteins: A2ASA8, A2CI98, A2CJ06, A4IG61, A4IIW0, A7MB64, A8E4S7, O15482, P59025, P79621, Q08AI8, Q0IES7, Q0IES8, Q0V9X7, Q29H55, Q29H56, Q3TNL8, Q3UJB3, Q3UPR7, Q567X9, Q569B5, Q5MYT7, Q5QGT7, Q5TW90, Q640Z9, Q66H52, Q6DCQ5, Q6GNM3, Q6GPH6, Q6GQ81, Q6GQD9, Q6NYB4, Q7QHX4, Q80VA5, Q80ZF2, Q80ZI2, Q8BPP1, Q8C8C1, Q8CEZ4, Q8CI17

Diamond homologs: Q08AI8, Q8CEZ4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3148872	GRCh37/hg19 2q37.3(chr2:239671606-242782258)x1	Pathogenic

SpliceAI

1266 predictions. Top by Δscore:

Variant	Effect	Δscore
2:240888288:CCACC:C	donor_gain	1.0000
2:240888289:CA:C	donor_loss	1.0000
2:240888290:A:AC	donor_gain	1.0000
2:240888291:C:A	donor_loss	1.0000
2:240888291:C:CC	donor_gain	1.0000
2:240890000:GGTAC:G	donor_loss	1.0000
2:240890001:GTA:G	donor_loss	1.0000
2:240895479:TGTAC:T	donor_loss	1.0000
2:240895480:GTACC:G	donor_loss	1.0000
2:240895481:TACCT:T	donor_loss	1.0000
2:240895482:AC:A	donor_loss	1.0000
2:240895483:C:T	donor_loss	1.0000
2:240887161:AAC:A	acceptor_loss	0.9900
2:240887163:C:CC	acceptor_gain	0.9900
2:240888290:AC:A	donor_gain	0.9900
2:240888291:CC:C	donor_gain	0.9900
2:240888616:C:CT	acceptor_gain	0.9900
2:240888645:CCAT:C	acceptor_gain	0.9900
2:240888646:CATC:C	acceptor_gain	0.9900
2:240888648:TC:T	acceptor_loss	0.9900
2:240888649:C:CA	acceptor_loss	0.9900
2:240888649:C:CC	acceptor_gain	0.9900
2:240891532:GCCTA:G	donor_loss	0.9900
2:240891533:CCTA:C	donor_loss	0.9900
2:240891534:CTA:C	donor_loss	0.9900
2:240891535:TAC:T	donor_loss	0.9900
2:240891536:ACCT:A	donor_gain	0.9900
2:240891537:C:A	donor_loss	0.9900
2:240891537:CCTC:C	donor_gain	0.9900
2:240891656:T:TA	donor_gain	0.9900

AlphaMissense

2885 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:240895828:A:G	F57S	0.991
2:240891542:A:G	W246R	0.984
2:240891542:A:T	W246R	0.984
2:240895827:G:C	F57L	0.983
2:240895827:G:T	F57L	0.983
2:240895829:A:G	F57L	0.983
2:240888448:G:C	F365L	0.978
2:240888448:G:T	F365L	0.978
2:240888450:A:G	F365L	0.978
2:240890086:G:C	S271R	0.978
2:240890086:G:T	S271R	0.978
2:240890088:T:G	S271R	0.978
2:240890052:A:G	W283R	0.976
2:240890052:A:T	W283R	0.976
2:240888310:G:C	F411L	0.974
2:240888310:G:T	F411L	0.974
2:240888312:A:G	F411L	0.974
2:240891540:C:A	W246C	0.973
2:240891540:C:G	W246C	0.973
2:240895523:C:G	A159P	0.973
2:240895564:G:T	P145H	0.969
2:240888619:G:C	F308L	0.968
2:240888619:G:T	F308L	0.968
2:240888621:A:G	F308L	0.968
2:240891670:G:T	P203H	0.968
2:240888449:A:G	F365S	0.967
2:240895631:A:G	W123R	0.966
2:240895631:A:T	W123R	0.966
2:240891681:G:C	F199L	0.963
2:240891681:G:T	F199L	0.963

dbSNP variants (sampled 300 via entrez): RS1000048060 (2:240888003 G>T), RS1000161998 (2:240887721 G>C), RS1000189270 (2:240885755 T>C,G), RS1000197132 (2:240892415 C>T), RS1000277078 (2:240886095 G>A), RS1000330866 (2:240896989 C>T), RS1000913547 (2:240894480 G>A), RS1001102071 (2:240888723 C>T), RS1001153962 (2:240893420 A>T), RS1001335972 (2:240898009 T>G), RS1001618367 (2:240888555 A>G), RS1001629971 (2:240898303 T>C,G), RS1001763181 (2:240898070 C>T), RS1001891780 (2:240897828 C>T), RS1002274344 (2:240894198 T>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

7 associations (top):

Study	Trait	p-value
GCST003998_4	Joint mobility (Beighton score)	6.000000e-12
GCST004067_100	Hip circumference adjusted for BMI	1.000000e-08
GCST004067_32	Hip circumference adjusted for BMI	2.000000e-09
GCST005547_5	Major depressive disorder	6.000000e-08
GCST007429_73	Lung function (FVC)	1.000000e-13
GCST007432_12	FEV1	1.000000e-06
GCST90020028_710	Hip circumference adjusted for BMI	1.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007905	joint hypermobility measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004312	vital capacity
EFO:0004314	forced expiratory volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
Acetaminophen	decreases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	3
sodium arsenite	increases expression, decreases expression	2
(+)-JQ1 compound	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
OTX015	decreases expression	1
mivebresib	decreases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
dinophysistoxin 1	decreases expression	1
tebuconazole	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Catechin	affects cotreatment, increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases expression	1
Asbestos, Crocidolite	increases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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