TMEM121B

Summary

TMEM121B (transmembrane protein 121B, HGNC:1844) is a protein-coding gene on chromosome 22q11.1, encoding Transmembrane protein 121B (Q9BXQ6).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 99 total — 1 pathogenic
• MANE Select transcript: NM_031890

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1844
Approved symbol	TMEM121B
Name	transmembrane protein 121B
Location	22q11.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183307
Ensembl biotype	protein_coding
Entrez	27439

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000331437, ENST00000399875

RefSeq mRNA: 2 — MANE Select: NM_031890 NM_001163079, NM_031890

CCDS: CCDS13740, CCDS54494

Canonical transcript exons

ENST00000331437 — 1 exons

Exon	Start	End
ENSE00001310406	17116297	17121360

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 87.41.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0495 / max 58.1901, expressed in 509 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193065	1.5926	474
193064	0.2792	174
193063	0.1778	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	87.41	gold quality
prefrontal cortex	UBERON:0000451	81.20	gold quality
ganglionic eminence	UBERON:0004023	80.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.07	gold quality
frontal cortex	UBERON:0001870	77.72	gold quality
monocyte	CL:0000576	77.51	gold quality
leukocyte	CL:0000738	77.49	gold quality
right frontal lobe	UBERON:0002810	77.33	gold quality
neocortex	UBERON:0001950	77.09	gold quality
granulocyte	CL:0000094	76.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.17	gold quality
cerebral cortex	UBERON:0000956	75.61	gold quality
anterior cingulate cortex	UBERON:0009835	74.91	gold quality
middle temporal gyrus	UBERON:0002771	74.71	silver quality
primary visual cortex	UBERON:0002436	74.62	gold quality
caudate nucleus	UBERON:0001873	74.23	gold quality
cerebellar hemisphere	UBERON:0002245	73.91	gold quality
cerebellar cortex	UBERON:0002129	73.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.83	gold quality
putamen	UBERON:0001874	73.74	gold quality
nucleus accumbens	UBERON:0001882	73.65	gold quality
cerebellum	UBERON:0002037	72.97	gold quality
forebrain	UBERON:0001890	71.97	gold quality
blood	UBERON:0000178	71.50	gold quality
brain	UBERON:0000955	71.36	gold quality
superior frontal gyrus	UBERON:0002661	70.91	gold quality
Ammon’s horn	UBERON:0001954	70.76	gold quality
occipital lobe	UBERON:0002021	70.58	gold quality
amygdala	UBERON:0001876	70.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

154 targeting TMEM121B, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4645-5P	99.98	65.81	1284
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-3148	99.97	75.06	6478
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-9983-3P	99.94	71.48	3631

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem121b	ENSDARG00000087319
mus_musculus	Tmem121b	ENSMUSG00000094626
rattus_norvegicus	Tmem121b	ENSRNOG00000087372
caenorhabditis_elegans		WBGENE00008760

Paralogs (1): CIMIP2B (ENSG00000215187)

Protein

Protein identifiers

Transmembrane protein 121B — Q9BXQ6 (reviewed: Q9BXQ6)

Alternative names: Cat eye syndrome critical region protein 6

All UniProt accessions (1): Q9BXQ6

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Widely expressed, especially in adult heart, brain, prostate, testes, peripherical blood leukocytes and fetal brain.

Miscellaneous. Candidate gene for the Cat Eye Syndrome (CES), a developmental disorder associated with the duplication of a 2 Mb region of 22q11.2. Duplication usually takes in the form of a surpernumerary bisatellited isodicentric chromosome, resulting in four copies of the region (represents an inv dup(22)(q11)). CES is characterized clinically by the combination of coloboma of the iris and anal atresia with fistula, downslanting palpebral fissures, preauricular tags and/or pits, frequent occurrence of heart and renal malformations, and normal or near-normal mental development.

Similarity. Belongs to the TMEM121 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BXQ6-1	1	yes
Q9BXQ6-2	2

RefSeq proteins (2): NP_001156551, NP_114096* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026624	CECR6	Family
IPR032776	CECR6/TMEM121	Family

Pfam: PF14997

UniProt features (11 total): compositionally biased region 4, region of interest 3, modified residue 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXQ6-F1	61.31	0.16

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 (2): 167, 552

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): MODULE_255, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MODULE_317, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, MODULE_69, BOCHKIS_FOXA2_TARGETS, MEISSNER_NPC_HCP_WITH_H3K4ME2, PHESSE_TARGETS_OF_APC_AND_MBD2_UP, CERIBELLI_PROMOTERS_INACTIVE_AND_BOUND_BY_NFY, BILANGES_SERUM_AND_RAPAMYCIN_SENSITIVE_GENES, MODULE_37, CHAF1A_TARGET_GENES, ID2_TARGET_GENES, ZNF391_TARGET_GENES, MIR30D_5P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM121B	SLC35E4	Q6ICL7	560
TMEM121B	HDHD5	Q9BXW7	547
TMEM121B	LHFPL4	Q7Z7J7	543
TMEM121B	ATP5MGL	Q7Z4Y8	449
TMEM121B	RIMBP3B	A6NNM3	447
TMEM121B	IKZF4	Q9H2S9	441
TMEM121B	TBX18	O95935	427
TMEM121B	MICAL3	Q7RTP6	397
TMEM121B	KLHL36	Q8N4N3	397
TMEM121B	RIMBP3C	A6NJZ7	390
TMEM121B	CECR2	Q9BXF3	390
TMEM121B	ZNF492	Q9P255	390
TMEM121B	RABAC1	Q9UI14	381
TMEM121B	LHFPL3	Q86UP9	373
TMEM121B	POTEH	Q6S545	351

IntAct

0 interactions, top by confidence:

BioGRID (7): CECR6 (Negative Genetic), CECR6 (Protein-peptide), CECR6 (Co-fractionation), CECR6 (Co-fractionation), CECR6 (Co-fractionation), CECR6 (Co-fractionation), CECR6 (Affinity Capture-MS)

ESM2 similar proteins: A6NKL6, A6NNE9, A6P320, D3YYI7, E9Q0B3, F5H4A9, O60346, P0C1G7, P0C7U0, P0DPB3, P39881, P53349, Q0P496, Q13233, Q147X3, Q2TBI2, Q3TZ87, Q49LS4, Q52L14, Q5GH59, Q5GH67, Q5GH76, Q5VV17, Q62925, Q66JB6, Q6NS60, Q80TE3, Q86VE0, Q86YJ5, Q8BGW2, Q8CBH7, Q8R554, Q8TC41, Q8TE49, Q8TF61, Q96EP1, Q96SQ7, Q99MX7, Q99NA2, Q9BXQ6

Diamond homologs: Q99MX7, Q9BXQ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	94
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625581	GRCh37/hg19 22q11.1-11.21(chr22:17289827-17938918)	Pathogenic

SpliceAI

236 predictions. Top by Δscore:

Variant	Effect	Δscore
22:17119479:C:CA	donor_gain	0.9500
22:17119528:AGCCC:A	donor_gain	0.8400
22:17118797:C:CT	acceptor_gain	0.8200
22:17119440:C:A	donor_gain	0.8000
22:17118798:A:T	acceptor_gain	0.7700
22:17119385:TC:T	donor_gain	0.7700
22:17118797:C:T	acceptor_gain	0.7500
22:17119660:C:CT	donor_gain	0.7500
22:17120419:C:CT	donor_gain	0.7300
22:17119426:AG:A	donor_gain	0.7200
22:17119661:C:CT	donor_gain	0.6900
22:17120145:T:TG	acceptor_gain	0.6900
22:17118801:C:CT	acceptor_gain	0.6000
22:17119381:CCCT:C	donor_gain	0.6000
22:17120420:C:CT	donor_gain	0.6000
22:17118802:A:T	acceptor_gain	0.5900
22:17120140:C:CT	donor_gain	0.5900
22:17119581:T:TA	donor_gain	0.5600
22:17120146:T:A	acceptor_gain	0.5600
22:17119590:T:TA	donor_gain	0.5400
22:17120141:C:CT	donor_gain	0.5400
22:17119427:G:C	donor_gain	0.5100
22:17120141:CACCT:C	acceptor_gain	0.5000
22:17119528:AGCC:A	donor_gain	0.4800
22:17119658:G:T	donor_gain	0.4800
22:17118679:GAGC:G	acceptor_gain	0.4700
22:17119382:CCT:C	donor_gain	0.4600
22:17119695:TCC:T	donor_gain	0.4600
22:17120265:G:A	donor_gain	0.4600
22:17120819:GCCCA:G	donor_loss	0.4600

AlphaMissense

3630 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:17120144:C:A	K328N	0.999
22:17120144:C:G	K328N	0.999
22:17120148:G:T	P327H	0.999
22:17120176:A:G	W318R	0.999
22:17120176:A:T	W318R	0.999
22:17120407:A:G	W241R	0.999
22:17120407:A:T	W241R	0.999
22:17120427:T:A	D234V	0.999
22:17120427:T:G	D234A	0.999
22:17120438:C:A	W230C	0.999
22:17120438:C:G	W230C	0.999
22:17120440:A:G	W230R	0.999
22:17120440:A:T	W230R	0.999
22:17120472:A:G	L219P	0.999
22:17119622:C:A	K502N	0.998
22:17119622:C:G	K502N	0.998
22:17119910:G:C	S406R	0.998
22:17119910:G:T	S406R	0.998
22:17119912:T:G	S406R	0.998
22:17120046:G:C	P361R	0.998
22:17120433:G:T	A232D	0.998
22:17120472:A:T	L219H	0.998
22:17119920:A:G	L403P	0.997
22:17120046:G:T	P361H	0.997
22:17120073:A:G	F352S	0.997
22:17120136:A:G	L331P	0.997
22:17120148:G:C	P327R	0.997
22:17120157:G:T	A324D	0.997
22:17120409:C:T	G240D	0.997
22:17120427:T:C	D234G	0.997

dbSNP variants (sampled 300 via entrez): RS1001502200 (22:17123311 A>G), RS1002541299 (22:17121588 G>A,C), RS1003135404 (22:17120378 C>A,T), RS1003514001 (22:17120640 C>G,T), RS1004092343 (22:17119299 A>C,G,T), RS1004571399 (22:17119011 A>T), RS1005169281 (22:17117437 C>T), RS1005503845 (22:17117790 G>C), RS1005563123 (22:17122264 A>G), RS1006098671 (22:17116232 A>G), RS1006587815 (22:17115964 G>A,C), RS1006601271 (22:17120696 C>A,G,T), RS1007026000 (22:17120935 C>A,T), RS1007620527 (22:17119599 C>A,T), RS1008680260 (22:17117912 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:115470

GenCC curated gene-disease

Mondo (1): cat-eye syndrome (MONDO:0007276)

Orphanet (1): Cat-eye syndrome (Orphanet:195)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002579_27	Heschl’s gyrus morphology	2.000000e-06
GCST003437_2	Discordance in emotional problems in monozygotic twins	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007803	emotional symptom measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535918	Schmid-Fraccaro syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases reaction, increases expression, affects cotreatment, decreases reaction, affects binding (+1 more)	4
Valproic Acid	decreases expression, increases methylation, affects cotreatment	3
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
arsenite	increases methylation	1
3,3’-diindolylmethane	increases reaction, increases expression, affects reaction, decreases reaction, affects binding	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Norethindrone Acetate	increases expression, affects cotreatment	1
Calcitriol	increases expression, affects cotreatment	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Tamoxifen	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02067806	Not specified	COMPLETED	Observational Study on 2-chloroprocaine Hydrochloride 1%
NCT04465136	Not specified	TERMINATED	CES in the Elderly With Generalized Anxiety Disorders