PATL2

Summary

PATL2 (PAT1 homolog 2, HGNC:33630) is a protein-coding gene on chromosome 15q21.1, encoding Protein PAT1 homolog 2 (C9JE40). RNA-binding protein that acts as a translational repressor.

Predicted to enable RNA binding activity. Predicted to be involved in P-body assembly; deadenylation-dependent decapping of nuclear-transcribed mRNA; and negative regulation of translation. Predicted to act upstream of or within negative regulation of cytoplasmic mRNA processing body assembly. Located in cytoplasm.

Source: NCBI Gene 197135 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oocyte maturation defect 4 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 101 total — 9 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 8
• MANE Select transcript: NM_001387263

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33630
Approved symbol	PATL2
Name	PAT1 homolog 2
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	Pat1a
Ensembl gene	ENSG00000229474
Ensembl biotype	protein_coding
OMIM	614661
Entrez	197135

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000434130, ENST00000558159, ENST00000558481, ENST00000558573, ENST00000558809, ENST00000560110, ENST00000560780, ENST00000561082, ENST00000682850, ENST00000890223, ENST00000890224, ENST00000890225, ENST00000890226, ENST00000890227, ENST00000890228, ENST00000941555, ENST00000941556

RefSeq mRNA: 7 — MANE Select: NM_001387263 NM_001145112, NM_001330283, NM_001387260, NM_001387261, NM_001387262, NM_001387263, NM_001387264

CCDS: CCDS45253, CCDS81873

Canonical transcript exons

ENST00000682850 — 18 exons

Exon	Start	End
ENSE00001605093	44675486	44675691
ENSE00001623557	44672015	44672156
ENSE00001666821	44667106	44667203
ENSE00001709743	44669280	44669413
ENSE00001724124	44668342	44668482
ENSE00001784384	44669777	44669874
ENSE00001785023	44668980	44669139
ENSE00001795751	44669510	44669563
ENSE00002559621	44665732	44665971
ENSE00003468632	44674150	44674230
ENSE00003544456	44673235	44673377
ENSE00003556862	44672388	44672456
ENSE00003615855	44669967	44670087
ENSE00003655003	44666392	44666541
ENSE00003683236	44676475	44676565
ENSE00003920485	44710871	44710929
ENSE00003921810	44710096	44710214
ENSE00003922352	44711020	44711323

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 97.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5392 / max 535.0233, expressed in 1195 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149665	9.0510	1185
149663	0.5750	91
149661	0.2954	66
149660	0.2364	58
149659	0.1806	50
149664	0.1555	87
149658	0.0453	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.42	gold quality
oocyte	CL:0000023	96.81	gold quality
secondary oocyte	CL:0000655	94.85	gold quality
spleen	UBERON:0002106	91.37	gold quality
blood	UBERON:0000178	88.93	gold quality
lymph node	UBERON:0000029	86.27	gold quality
vermiform appendix	UBERON:0001154	85.06	gold quality
bone marrow cell	CL:0002092	82.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.15	gold quality
right lung	UBERON:0002167	81.70	gold quality
leukocyte	CL:0000738	80.81	gold quality
monocyte	CL:0000576	80.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.05	gold quality
small intestine	UBERON:0002108	78.76	gold quality
right uterine tube	UBERON:0001302	78.67	gold quality
right adrenal gland cortex	UBERON:0035827	77.47	gold quality
right adrenal gland	UBERON:0001233	77.25	gold quality
upper lobe of left lung	UBERON:0008952	77.16	gold quality
rectum	UBERON:0001052	76.65	gold quality
left adrenal gland cortex	UBERON:0035825	76.62	gold quality
gall bladder	UBERON:0002110	76.56	gold quality
left adrenal gland	UBERON:0001234	76.14	gold quality
caecum	UBERON:0001153	75.50	gold quality
right lobe of liver	UBERON:0001114	75.41	gold quality
bronchial epithelial cell	CL:0002328	75.18	gold quality
bone marrow	UBERON:0002371	75.05	gold quality
ileal mucosa	UBERON:0000331	74.87	silver quality
upper lobe of lung	UBERON:0008948	74.69	gold quality
adrenal cortex	UBERON:0001235	74.50	gold quality
bronchus	UBERON:0002185	74.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting PATL2, 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-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-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-3144-3P	98.15	67.34	677
HSA-MIR-4423-3P	97.98	69.66	912
HSA-MIR-3622A-5P	97.43	67.11	356
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-4791	96.51	67.76	659

Literature-anchored findings (GeneRIF, showing 11)

• Mutation in PATL2 gene is associated with Female Infertility. (PMID:28965844)
• Nonsense mutation in PATL2 gene is associated with Female Infertility. (PMID:28965849)
• Data indicate PAT1 homolog 2 protein (PATL2) mutation as a major cause of oocyte meiotic deficiency. (PMID:29661911)
• this study confirms previous findings that PATL2 is required for human oocyte maturation and female fertility, and also indicates the potential prognostic value of testing for PATL2 mutations in infertile women with oocyte germinal vesicle arrest. (PMID:29697801)
• This work further indicates the critical role of PATL2 in oocyte maturation and early embryo development and will provide a basis for pursuing the determination of genetic variation in PALT2 as an additional criterion for evaluating the quality of oocytes and embryos for assisted reproduction techniques. (PMID:30765866)
• Novel homozygous mutations in PATL2 lead to female infertility with oocyte maturation arrest. (PMID:32048119)
• PATL2 regulated the apoptosis of ovarian granulosa cells in patients with PCOS. (PMID:34008465)
• Novel mutations in NLRP5 and PATL2 cause female infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest. (PMID:35091966)
• Reduced PATL2 Impairs the Proliferation of Ovarian Granulosa Cells by Decreasing ADM2 Expression in Patients with PCOS. (PMID:38087182)
• Identification novel mutations and phenotypic spectrum expanding in PATL2 in infertile women with IVF/ICSI failure. (PMID:38536595)
• Novel PATL2 variants cause female infertility with oocyte maturation defect. (PMID:38954294)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	patl2	ENSDARG00000089567
mus_musculus	Patl2	ENSMUSG00000027233
rattus_norvegicus	Patl2	ENSRNOG00000017061
drosophila_melanogaster	Patr-1	FBGN0266053
caenorhabditis_elegans		WBGENE00009661

Paralogs (1): PATL1 (ENSG00000166889)

Protein

Protein identifiers

Protein PAT1 homolog 2 — C9JE40 (reviewed: C9JE40)

Alternative names: PAT1-like protein 2, Protein PAT1 homolog a

All UniProt accessions (5): C9JE40, H0YMQ2, H0YMS5, H0YN77, H0YNY1

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that acts as a translational repressor.

Subunit / interactions. Interacts with LSM1.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in oocytes.

Disease relevance. Oocyte/zygote/embryo maturation arrest 4 (OZEMA4) [MIM:617743] An autosomal recessive infertility disorder characterized by oocyte maturation arrest that can occur at different stages of maturation. Some oocytes exhibit maturation arrest at the germinal vesicle stage and others at the metaphase I stage. Oocytes progressing to polar body I either undergo fertilization failure or, in those that are fertilized, early embryonic arrest. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the PAT1 family.

RefSeq proteins (7): NP_001138584, NP_001317212, NP_001374189, NP_001374190, NP_001374191, NP_001374192, NP_001374193 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019167	PAT1_dom	Domain
IPR039900	Pat1-like	Family

Pfam: PF09770

UniProt features (16 total): sequence variant 11, region of interest 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-C9JE40-F1	65.05	0.12

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): GOBP_P_BODY_ASSEMBLY, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_ORGANELLE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_DEADENYLATION_DEPENDENT_DECAY, GOBP_REGULATION_OF_ORGANELLE_ASSEMBLY

GO Biological Process (4): deadenylation-dependent decapping of nuclear-transcribed mRNA (GO:0000290), negative regulation of cytoplasmic mRNA processing body assembly (GO:0010607), negative regulation of translation (GO:0017148), P-body assembly (GO:0033962)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (4): P-body (GO:0000932), nucleus (GO:0005634), cytoplasm (GO:0005737), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
nuclear-transcribed mRNA catabolic process	1
mRNA methylguanosine-cap decapping	1
regulation of cytoplasmic mRNA processing body assembly	1
P-body assembly	1
negative regulation of organelle assembly	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
membraneless organelle assembly	1
nucleic acid binding	1
binding	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

860 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PATL2	LSM14B	Q9BX40	786
PATL2	TUBB8	Q3ZCM7	720
PATL2	EIF4ENIF1	Q9NRA8	713
PATL2	WEE2	P0C1S8	711
PATL2	DDX6	P26196	694
PATL2	TLE6	Q9H808	672
PATL2	NLRP5	P59047	524
PATL2	KHDC3L	Q587J8	506
PATL2	PADI6	Q6TGC4	501
PATL2	DCP2	Q8IU60	488
PATL2	EDC3	Q96F86	476
PATL2	APPBP2	Q92624	467
PATL2	LSM1	O15116	465
PATL2	EIF4E1B	A6NMX2	454
PATL2	XRN1	Q8IZH2	450

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PATL2	RRBP1	psi-mi:“MI:0915”(physical association)	0.400
PATL2	DNAH5	psi-mi:“MI:0915”(physical association)	0.400
PATL2	LSM1	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): DNAH5 (Proximity Label-MS), RRBP1 (Proximity Label-MS), PATL2 (Co-fractionation), PATL2 (Affinity Capture-RNA)

ESM2 similar proteins: A0JN53, A1L3T7, C9JE40, D2I4M3, G3HQ82, O43299, O75800, O94812, P58660, Q0P5G1, Q15572, Q1RMI8, Q1W1Y5, Q3T1I9, Q3U829, Q56B11, Q571B6, Q58CQ5, Q5ND34, Q5R8S0, Q66H85, Q6NZL6, Q6ZNJ1, Q6ZQA0, Q76MJ5, Q80TE0, Q80UU1, Q80UW5, Q8BGI5, Q8BMG1, Q8C3R1, Q8C3S2, Q8C7B8, Q8CE13, Q8IZL8, Q8N163, Q8VDP4, Q8WXE1, Q96HA7, Q9BQG0

Diamond homologs: A2ARM1, A2RRV3, B5DEB9, B5DF93, C9JE40, Q32N92, Q3TC46, Q4V7K4, Q5R8Q4, Q86TB9, A8WSQ9, Q20374

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	6
Uncertain significance	64
Likely benign	13
Benign	4

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1323414	NM_001387263.1(PATL2):c.1225-2A>G	Pathogenic
1459028	NC_000015.9:g.(?44864989)(44988554_?)del	Pathogenic
2499466	NM_001387263.1(PATL2):c.890del (p.Ala297fs)	Pathogenic
3257188	NM_001387263.1(PATL2):c.516-2A>G	Pathogenic
444048	NM_001387263.1(PATL2):c.558T>A (p.Tyr186Ter)	Pathogenic
444049	NM_001387263.1(PATL2):c.223-14_223-2del	Pathogenic
444050	NM_001387263.1(PATL2):c.1224+2T>C	Pathogenic
4813487	NM_001387263.1(PATL2):c.437dup (p.Pro146_Arg147insTer)	Pathogenic
4813494	NM_001387263.1(PATL2):c.310del (p.Asp104fs)	Pathogenic
1324847	NM_001387263.1(PATL2):c.446+1G>C	Likely pathogenic
3391143	NM_001387263.1(PATL2):c.135TCTGGACCCAGA[1] (p.47DPDL[1])	Likely pathogenic
444047	NM_001387263.1(PATL2):c.784C>T (p.Arg262Ter)	Likely pathogenic
4845685	NM_001387263.1(PATL2):c.911dup (p.Leu305fs)	Likely pathogenic
549488	NM_001387263.1(PATL2):c.649T>A (p.Tyr217Asn)	Likely pathogenic
549492	NM_001387263.1(PATL2):c.566T>G (p.Leu189Arg)	Likely pathogenic

SpliceAI

2176 predictions. Top by Δscore:

Variant	Effect	Δscore
15:44666390:A:AC	donor_gain	1.0000
15:44666390:ACT:A	donor_gain	1.0000
15:44666391:C:CC	donor_gain	1.0000
15:44666391:CT:C	donor_gain	1.0000
15:44666391:CTC:C	donor_gain	1.0000
15:44667204:C:CC	acceptor_gain	1.0000
15:44669135:CCTCT:C	acceptor_gain	1.0000
15:44669136:CTCT:C	acceptor_gain	1.0000
15:44669136:CTCTC:C	acceptor_gain	1.0000
15:44669137:TCTCT:T	acceptor_gain	1.0000
15:44669138:CT:C	acceptor_gain	1.0000
15:44669140:C:CC	acceptor_gain	1.0000
15:44669278:A:AC	donor_gain	1.0000
15:44669278:ACT:A	donor_gain	1.0000
15:44669279:C:CC	donor_gain	1.0000
15:44669279:CT:C	donor_gain	1.0000
15:44669279:CTC:C	donor_gain	1.0000
15:44669872:CCA:C	acceptor_gain	1.0000
15:44669873:CAC:C	acceptor_gain	1.0000
15:44669875:C:CC	acceptor_gain	1.0000
15:44669966:CCGGA:C	donor_gain	1.0000
15:44669974:ATAAG:A	donor_gain	1.0000
15:44669976:AAG:A	donor_gain	1.0000
15:44670006:CCAG:C	donor_gain	1.0000
15:44670022:AAC:A	donor_gain	1.0000
15:44670023:A:C	donor_gain	1.0000
15:44670083:TATTC:T	acceptor_gain	1.0000
15:44670084:ATTC:A	acceptor_gain	1.0000
15:44670085:TTC:T	acceptor_gain	1.0000
15:44670086:TC:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000096847 (15:44672158 T>C), RS1000154977 (15:44689886 T>C,G), RS1000160470 (15:44699613 C>T), RS1000214871 (15:44699939 T>C), RS1000219847 (15:44712011 C>T), RS1000223941 (15:44706850 TC>T), RS1000272307 (15:44711761 G>A,C), RS1000335992 (15:44674300 T>C), RS1000388274 (15:44674568 TAAA>T,TAA,TAAAA), RS1000400696 (15:44679388 C>A,T), RS1000408327 (15:44692226 G>A,C), RS1000466721 (15:44686062 T>C), RS1000507349 (15:44705456 A>G), RS1000534981 (15:44705343 C>T), RS1000549660 (15:44666194 C>A,T)

Disease associations

OMIM: gene MIM:614661 | disease phenotypes: MIM:617743, MIM:604360

GenCC curated gene-disease

Disease	Classification	Inheritance
oocyte maturation defect 4	Strong	Autosomal recessive

Mondo (2): oocyte maturation defect 4 (MONDO:0021575), hereditary spastic paraplegia 11 (MONDO:0011445)

Orphanet (1): Autosomal recessive spastic paraplegia type 11 (Orphanet:2822)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000147	Polycystic ovaries
HP:0008222	Female infertility
HP:0008669	Abnormal spermatogenesis
HP:0011462	Young adult onset
HP:0020155	Abnormal oocyte morphology
HP:0031515	Abnormal meiosis
HP:0031516	Metaphase I oocyte maturation arrest

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007726_4	Anti-Toxoplasma gondii IgG seropositivity	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007047	Toxoplasma gondii seropositivity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases mutagenesis	3
bisphenol A	increases methylation	1
sodium arsenite	decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases abundance, decreases methylation	1
Catechin	affects cotreatment, decreases expression	1
Nitrogen Oxides	decreases methylation, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7EU	AMUFAHi003-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia