TGIF2LY

Summary

TGIF2LY (TGFB induced factor homeobox 2 like Y-linked, HGNC:18569) is a protein-coding gene on chromosome Yp11.2, encoding Homeobox protein TGIF2LY (Q8IUE0). May have a transcription role in testis.

This gene encodes a member of the TALE/TGIF homeobox family of transcription factors. This gene lies within the male specific region of chromosome Y, in a block of sequence that is thought to be the result of a large X-to-Y transposition. The C-terminus of this protein is divergent from that of its chromosome X homolog (TGIF2LX), suggesting that this protein may act as a regulator of TGIF2LX.

Source: NCBI Gene 90655 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 9 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_139214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18569
Approved symbol	TGIF2LY
Name	TGFB induced factor homeobox 2 like Y-linked
Location	Yp11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176679
Ensembl biotype	protein_coding
OMIM	400025
Entrez	90655

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000321217, ENST00000559055

RefSeq mRNA: 1 — MANE Select: NM_139214 NM_139214

CCDS: CCDS14775

Canonical transcript exons

ENST00000321217 — 2 exons

Exon	Start	End
ENSE00001091887	3579067	3579127
ENSE00001889836	3579224	3580041

Expression profiles

Bgee: expression breadth tissue_specific, 7 present calls, max score 86.77.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.58	gold quality
testis	UBERON:0000473	62.44	gold quality
left testis	UBERON:0004533	61.65	gold quality
right testis	UBERON:0004534	59.29	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.36	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
right coronary artery	UBERON:0001625	27.84	gold quality
lymph node	UBERON:0000029	27.57	gold quality
leukocyte	CL:0000738	27.54	gold quality
monocyte	CL:0000576	27.53	gold quality
primary visual cortex	UBERON:0002436	27.27	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.16

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1572.1	TGIF2LY	TALE-type homeo domain factors

JASPAR matrix evidence (PMIDs): PMID:8537382

miRNA regulators (miRDB)

18 targeting TGIF2LY, 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-4516	99.61	67.78	3390
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-2681-3P	98.18	65.28	577
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-12126	98.09	64.82	637
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-490-5P	96.75	65.81	661
HSA-MIR-6747-5P	96.17	64.99	743

Literature-anchored findings (GeneRIF, showing 2)

• Association of TGIFLX/Y mRNA expression with azoospermia in infertile men.( (PMID:18384077)
• most prostate tumors (73.5%) express at least one of these genes (TGIFLX and TGIFLY), although different patterns of mRNA expression were observed. These results suggest an association of TGIFLX/Y expression with the progression of prostate cancer. (PMID:18663611)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	pbx2	ENSDARG00000019717
danio_rerio	pbx4	ENSDARG00000052150
mus_musculus	Tgif2lx1	ENSMUSG00000100133
mus_musculus	Tgif2lx2	ENSMUSG00000100194
rattus_norvegicus	Tgif2lx2	ENSRNOG00000029850
drosophila_melanogaster	exd	FBGN0000611
drosophila_melanogaster	hth	FBGN0001235
drosophila_melanogaster	vis	FBGN0033748
drosophila_melanogaster	achi	FBGN0033749
caenorhabditis_elegans		WBGENE00000443
caenorhabditis_elegans		WBGENE00006796
caenorhabditis_elegans		WBGENE00017690

Paralogs (13): MEIS3 (ENSG00000105419), PBX4 (ENSG00000105717), TGIF2 (ENSG00000118707), MEIS2 (ENSG00000134138), MEIS1 (ENSG00000143995), TGIF2LX (ENSG00000153779), PKNOX1 (ENSG00000160199), PKNOX2 (ENSG00000165495), PBX3 (ENSG00000167081), TGIF1 (ENSG00000177426), PBX1 (ENSG00000185630), MEIS3P2 (ENSG00000188013), PBX2 (ENSG00000204304)

Protein

Protein identifiers

Homeobox protein TGIF2LY — Q8IUE0 (reviewed: Q8IUE0)

Alternative names: TGF-beta-induced transcription factor 2-like protein, TGFB-induced factor 2-like protein, Y-linked, TGIF-like on the Y

All UniProt accessions (1): Q8IUE0

UniProt curated annotations — full annotation on UniProt →

Function. May have a transcription role in testis. May act as a competitor/regulator of TGIF2LX.

Subcellular location. Nucleus.

Tissue specificity. Specifically expressed in adult testis.

Similarity. Belongs to the TALE/TGIF homeobox family.

RefSeq proteins (1): NP_631960* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR008422	KN_HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR050224	TALE_homeobox	Family

Pfam: PF05920

UniProt features (5 total): region of interest 2, chain 1, DNA-binding region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUE0-F1	69.27	0.29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 22 (showing top): ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chrYp11, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOMF_DNA_BINDING_TRANSCRIPTION_REPRESSOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GSE13485_CTRL_VS_DAY1_YF17D_VACCINE_PBMC_DN, GSE15659_NAIVE_CD4_TCELL_VS_RESTING_TREG_DN, GSE15659_CD45RA_NEG_CD4_TCELL_VS_RESTING_TREG_DN, FOURATI_BLOOD_TWINRIX_AGE_25_83YO_RESPONDERS_VS_POOR_RESPONDERS_0DY_DN, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, PULVER_FOREY_PERTURB_ACCUMULATION_G2_M, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TGIF2LY	PABPC5	Q96DU9	930
TGIF2LY	PCDH11X	Q9BZA7	887
TGIF2LY	TGFBI	Q15582	846
TGIF2LY	A0A087WUC5	A0A087WUC5	703
TGIF2LY	VCY	O14598	621
TGIF2LY	A6NEC3	A6NEC3	581
TGIF2LY	TSPY1	P09002	571
TGIF2LY	AMELY	Q99218	555
TGIF2LY	CDY2A	Q9Y6F7	546
TGIF2LY	TSPY4	P0CV99	545
TGIF2LY	PRKY	O43930	519
TGIF2LY	CDY1	Q9Y6F8	516
TGIF2LY	BPY2	O14599	506
TGIF2LY	HSFY1	Q96LI6	493
TGIF2LY	RBMY1B	A6NDE4	491

IntAct

18 interactions, top by confidence:

A	B	Type	Score
TGIF2LY	NAB2	psi-mi:“MI:0915”(physical association)	0.720
NAB2	TGIF2LY	psi-mi:“MI:0915”(physical association)	0.720
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
TGIF2LY	MBIP	psi-mi:“MI:0915”(physical association)	0.560
MBIP	TGIF2LY	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	LMNA	psi-mi:“MI:0914”(association)	0.560
HAUS1	BET1	psi-mi:“MI:0914”(association)	0.530
PCBD2	TGIF2LY	psi-mi:“MI:0915”(physical association)	0.370
NOTCH2NLA	IGKC	psi-mi:“MI:0914”(association)	0.350
TGIF2LX	TNRC18	psi-mi:“MI:0914”(association)	0.350
TGIF2LY	NAB2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (54): TGIF2LY (Two-hybrid), TGIF2LY (Two-hybrid), TGIF2LX (Affinity Capture-MS), LRP6 (Affinity Capture-MS), PDCD4 (Affinity Capture-MS), ANKHD1-EIF4EBP3 (Affinity Capture-MS), OGFR (Affinity Capture-MS), CRBN (Affinity Capture-MS), AHCYL2 (Affinity Capture-MS), PGP (Affinity Capture-MS), GMNN (Affinity Capture-MS), DCAF16 (Affinity Capture-MS), THNSL1 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), IRGQ (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTS1, A0A1B0GWH4, A1A4L6, A1YGI6, A6NDR6, B8QB46, F1MJR8, F1QDF8, O35892, O35893, P09015, P15036, P15037, P23497, P52729, P59598, Q32NH9, Q3KRF1, Q3UM89, Q4G112, Q4V7E1, Q5M7N6, Q5ND04, Q5XIV2, Q5ZHX5, Q66IG8, Q6P1R3, Q6PCX9, Q6PJQ5, Q708W2, Q76I76, Q76I79, Q76N89, Q7M6U3, Q8AXQ4, Q8BVK9, Q8IUE0, Q8IUE1, Q8IWB6, Q8IXJ9

Diamond homologs: A1YGI6, A6NDR6, A8K0S8, A8WL06, B7ZRT8, O00470, O04136, O14770, O22300, O42261, O46339, O65685, O70477, P41779, P41817, P46606, P48000, P48001, P48002, P48731, P53147, P54269, P55347, P56659, P56660, P56664, P56665, P56669, P70284, P78412, P78413, P78414, P78415, P79937, P81067, P81068, P97367, P97368, Q0E3C3, Q0J6N4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	5
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1703656	GRCh37/hg19 Yp11.31-11.2(chrY:2650140-7114097)	Pathogenic
2690971	NM_139214.3(TGIF2LY):c.534_535del (p.Leu179fs)	Likely pathogenic

SpliceAI

108 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:3579222:A:AG	acceptor_gain	0.9700
Y:3579223:G:GG	acceptor_gain	0.9700
Y:3579223:GTAAC:G	acceptor_gain	0.9600
Y:3579223:GT:G	acceptor_gain	0.9500
Y:3579246:T:TA	acceptor_gain	0.9500
Y:3579245:AT:A	acceptor_gain	0.9400
Y:3579125:CAGGT:C	donor_loss	0.9200
Y:3579128:G:GA	donor_loss	0.9200
Y:3579129:T:G	donor_loss	0.9200
Y:3579223:GTA:G	acceptor_gain	0.9100
Y:3579246:T:G	acceptor_gain	0.8900
Y:3579223:GTAA:G	acceptor_gain	0.8800
Y:3579248:G:C	acceptor_gain	0.8600
Y:3579246:TGG:T	acceptor_gain	0.8500
Y:3579244:TATGG:T	acceptor_gain	0.8400
Y:3579245:ATGGA:A	acceptor_gain	0.8400
Y:3579130:GAGAA:G	donor_loss	0.8300
Y:3579247:G:A	acceptor_gain	0.8200
Y:3579217:A:AG	acceptor_gain	0.8100
Y:3579221:T:G	acceptor_gain	0.7700
Y:3579221:TA:T	acceptor_loss	0.7500
Y:3579222:A:AC	acceptor_loss	0.7500
Y:3579209:T:TA	acceptor_loss	0.7400
Y:3579218:A:G	acceptor_gain	0.7300
Y:3579207:T:TA	acceptor_loss	0.7200
Y:3579246:TGGAG:T	acceptor_gain	0.7100
Y:3579247:GGAGG:G	acceptor_gain	0.7100
Y:3579220:A:AG	acceptor_gain	0.6900
Y:3579211:A:AG	acceptor_loss	0.6700
Y:3579248:G:T	acceptor_loss	0.6400

AlphaMissense

1212 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:3579545:T:C	F101L	0.986
Y:3579547:T:A	F101L	0.986
Y:3579547:T:G	F101L	0.986
Y:3579546:T:C	F101S	0.957
Y:3579448:G:C	W68C	0.954
Y:3579448:G:T	W68C	0.954
Y:3579542:T:A	W100R	0.954
Y:3579542:T:C	W100R	0.954
Y:3579544:G:C	W100C	0.954
Y:3579544:G:T	W100C	0.954
Y:3579464:T:C	F74L	0.939
Y:3579466:T:A	F74L	0.939
Y:3579466:T:G	F74L	0.939
Y:3579493:G:C	K83N	0.939
Y:3579493:G:T	K83N	0.939
Y:3579438:T:A	L65H	0.935
Y:3579446:T:A	W68R	0.935
Y:3579446:T:C	W68R	0.935
Y:3579476:C:T	P78S	0.931
Y:3579513:C:T	T90I	0.926
Y:3579564:G:C	R107P	0.924
Y:3579441:G:C	R66P	0.922
Y:3579546:T:G	F101C	0.922
Y:3579450:T:C	M69T	0.920
Y:3579557:C:A	R105S	0.919
Y:3579562:A:C	R106S	0.904
Y:3579562:A:T	R106S	0.904
Y:3579438:T:C	L65P	0.900
Y:3579519:T:C	L92S	0.899
Y:3579553:T:A	N103K	0.897

dbSNP variants (sampled 300 via entrez): RS1053786 (Y:3579810 A>G), RS1053787 (Y:3579826 A>G), RS1053788 (Y:3579837 T>A), RS1053790 (Y:3579874 T>C), RS1053791 (Y:3579923 C>G), RS112167115 (Y:3577672 A>T), RS112346061 (Y:3578280 C>T), RS1159760707 (Y:3579667 T>C), RS1177697814 (Y:3578549 A>T), RS1188148342 (Y:3579262 C>G), RS1198521244 (Y:3579658 C>A,T), RS1201007545 (Y:3579425 T>C), RS1209453421 (Y:3579779 C>T), RS1230924360 (Y:3577073 A>G), RS1233642961 (Y:3579552 A>G)

Disease associations

OMIM: gene MIM:400025 | disease phenotypes: MIM:400045

GenCC curated gene-disease

Mondo (1): 46,XX sex reversal 1 (MONDO:0100250)

Orphanet (1): Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	increases reaction, affects binding	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases expression, increases abundance	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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