FAM220A

Summary

FAM220A (family with sequence similarity 220 member A, HGNC:22422) is a protein-coding gene on chromosome 7p22.1, encoding Protein FAM220A (Q7Z4H9). Promotes dephosphorylation of transcriptional activator STAT3 by interacting with both STAT3 and protein phosphatase PTPN2.

Predicted to enable STAT family protein binding activity. Predicted to be involved in intracellular signal transduction and negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within protein dephosphorylation. Predicted to be located in acrosomal vesicle. Predicted to be active in nucleus.

Source: NCBI Gene 84792 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 11 total
• MANE Select transcript: NM_001037163

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22422
Approved symbol	FAM220A
Name	family with sequence similarity 220 member A
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	SIPAR, MGC12966, ACPIN1
Ensembl gene	ENSG00000178397
Ensembl biotype	protein_coding
OMIM	616628
Entrez	84792

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000313324, ENST00000524898, ENST00000530143, ENST00000533877

RefSeq mRNA: 1 — MANE Select: NM_001037163 NM_001037163

CCDS: CCDS34599

Canonical transcript exons

ENST00000313324 — 2 exons

Exon	Start	End
ENSE00002154575	6329411	6331235
ENSE00003842951	6348573	6348967

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3889 / max 160.1352, expressed in 1793 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82643	17.1443	1791
82642	0.2446	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.97	gold quality
sperm	CL:0000019	99.92	gold quality
oocyte	CL:0000023	99.89	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.93	gold quality
biceps brachii	UBERON:0001507	98.77	gold quality
quadriceps femoris	UBERON:0001377	98.60	gold quality
vastus lateralis	UBERON:0001379	98.60	gold quality
deltoid	UBERON:0001476	98.45	gold quality
tibialis anterior	UBERON:0001385	98.20	gold quality
adult organism	UBERON:0007023	97.47	gold quality
skeletal muscle tissue	UBERON:0001134	96.97	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.91	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.87	gold quality
left ventricle myocardium	UBERON:0006566	96.61	gold quality
middle temporal gyrus	UBERON:0002771	96.16	gold quality
cerebellar vermis	UBERON:0004720	95.98	gold quality
heart right ventricle	UBERON:0002080	95.57	gold quality
left testis	UBERON:0004533	95.45	gold quality
right testis	UBERON:0004534	95.32	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.31	gold quality
muscle tissue	UBERON:0002385	94.98	gold quality
testis	UBERON:0000473	94.63	gold quality
myocardium	UBERON:0002349	94.51	gold quality
skeletal muscle organ	UBERON:0014892	94.50	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.12	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.09	gold quality
gastrocnemius	UBERON:0001388	93.84	gold quality
muscle of leg	UBERON:0001383	93.59	gold quality
entorhinal cortex	UBERON:0002728	93.47	gold quality
epithelial cell of pancreas	CL:0000083	93.23	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	253.26
E-ANND-3	no	1.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting FAM220A, 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-4533	100.00	69.48	2758
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-4291	99.20	68.88	2969

Literature-anchored findings (GeneRIF, showing 1)

• results suggest that SIPAR terminates the activation of STAT3 through a dephosphorylation process that is dependent upon interaction with TC45 in the nucleus (PMID:26026268)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fam220a	ENSMUSG00000083012
rattus_norvegicus	Fam220a	ENSRNOG00000024605

Protein

Protein identifiers

Protein FAM220A — Q7Z4H9 (reviewed: Q7Z4H9)

Alternative names: STAT3-interacting protein as a repressor

All UniProt accessions (3): Q7Z4H9, E9PQC6, E9PQY0

UniProt curated annotations — full annotation on UniProt →

Function. Promotes dephosphorylation of transcriptional activator STAT3 by interacting with both STAT3 and protein phosphatase PTPN2. This promotes interaction of PTPN2 with STAT3 and mediates STAT3 dephosphorylation by PTPN2, leading to negative regulation of STAT3 transcriptional activator activity. May be required for spermiogenesis or sperm function.

Subunit / interactions. Interacts with transcriptional activator STAT3; the interaction occurs in both the nucleus and the cytoplasm, is enhanced by IL6 and promotes STAT3 dephosphorylation, leading to negative regulation of STAT3 transcriptional activator activity. Can interact with both unphosphorylated and phosphorylated STAT3 but interacts preferentially with phosphorylated STAT3 in the nucleus. Interacts with protein phosphatase PTPN2/TC45; this promotes interaction of PTPN2 with STAT3, leading to dephosphorylation of STAT3 by PTPN2.

Subcellular location. Nucleus. Cytoplasm. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

RefSeq proteins (1): NP_001032240* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029155	SIPAR	Domain
IPR040355	FAM220A	Family

Pfam: PF15487

UniProt features (9 total): sequence variant 5, region of interest 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4H9-F1	47.72	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): MODULE_255, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_317, IVANOVA_HEMATOPOIESIS_MATURE_CELL, chr7p22, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, OSMAN_BLADDER_CANCER_DN, GOCC_SECRETORY_VESICLE, MODULE_69, GOCC_ACROSOMAL_VESICLE, NUYTTEN_NIPP1_TARGETS_DN, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, BRUINS_UVC_RESPONSE_MIDDLE

GO Biological Process (1): negative regulation of transcription by RNA polymerase II (GO:0000122)

GO Molecular Function (2): STAT family protein binding (GO:0097677), protein binding (GO:0005515)

GO Cellular Component (4): acrosomal vesicle (GO:0001669), nucleus (GO:0005634), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
binding	1
secretory granule	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM220A	SPAG7	O75391	952
FAM220A	CD34	P28906	495
FAM220A	PAWR	Q96IZ0	449
FAM220A	OR51Q1	Q8NH59	447
FAM220A	TBCCD1	Q9NVR7	435
FAM220A	FAM222A	Q5U5X8	434
FAM220A	INTS15	Q96N11	434
FAM220A	ANKRD13D	Q6ZTN6	419
FAM220A	MYADML2	A6NDP7	417
FAM220A	C7orf25	Q9BPX7	412
FAM220A	UBALD1	Q8TB05	370
FAM220A	ZNF142	P52746	370
FAM220A	HERPUD2	Q9BSE4	331
FAM220A	DNHD1	Q96M86	327
FAM220A	ZNF12	P17014	316

IntAct

7 interactions, top by confidence:

A	B	Type	Score
FAM220A	TEKT4	psi-mi:“MI:0915”(physical association)	0.560
FAM220A	NEK6	psi-mi:“MI:0915”(physical association)	0.560
TEKT4	FAM220A	psi-mi:“MI:0915”(physical association)	0.000
NEK6	FAM220A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): FAM220A (Affinity Capture-Western), FAM220A (Reconstituted Complex), FAM220A (Two-hybrid), FAM220A (Two-hybrid), FAM220A (Protein-peptide)

ESM2 similar proteins: A0A1B0GUT2, A0A3Q1LFG5, A1L4Q6, A2RUQ5, A8MQB3, A8MU10, B1ANY3, C0HM98, H3BQW9, J3KSC0, P0C092, P0DMU3, P0DPA3, P24026, P59020, P59021, P59052, P87743, Q06250, Q0IIN9, Q0VFX4, Q14695, Q4R3X9, Q4VX62, Q52M75, Q5SR53, Q6ZUF6, Q6ZWC4, Q71F78, Q7Z4H9, Q8JMY5, Q8JMZ5, Q8JN06, Q8N2C9, Q8N2X6, Q8N3U1, Q8N9X3, Q8NAA6, Q8NBC4, Q8NDY4

Diamond homologs: B1ANY3, Q3ZN08, Q4R3X9, Q6DGF6, Q7Z4H9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

213 predictions. Top by Δscore:

Variant	Effect	Δscore
7:6348569:CCA:C	donor_loss	1.0000
7:6348570:CA:C	donor_loss	1.0000
7:6348571:A:AG	donor_loss	1.0000
7:6348572:CCT:C	donor_loss	1.0000
7:6348568:CCCA:C	donor_gain	0.9800
7:6348477:G:C	donor_gain	0.9600
7:6348571:A:AC	donor_gain	0.9600
7:6348572:C:CC	donor_gain	0.9600
7:6348634:AGCCG:A	donor_gain	0.9600
7:6338993:A:AC	donor_gain	0.9500
7:6338994:C:CC	donor_gain	0.9500
7:6338994:CTGTG:C	donor_gain	0.9400
7:6348572:CCTG:C	donor_gain	0.9400
7:6348634:AG:A	donor_gain	0.9400
7:6344051:A:T	donor_gain	0.9300
7:6348411:C:CT	donor_gain	0.9200
7:6348569:CCACC:C	donor_gain	0.9200
7:6348635:G:C	donor_gain	0.9200
7:6348471:CA:C	donor_gain	0.9100
7:6348571:ACC:A	donor_gain	0.9100
7:6348570:CAC:C	donor_gain	0.9000
7:6348572:C:CT	donor_gain	0.9000
7:6338989:A:C	donor_gain	0.8900
7:6344052:A:AC	donor_gain	0.8900
7:6344053:C:CC	donor_gain	0.8900
7:6348412:C:CT	donor_gain	0.8900
7:6344054:T:C	donor_gain	0.8800
7:6348573:C:T	donor_gain	0.8800
7:6332108:TCACG:T	acceptor_gain	0.8500
7:6348560:ACGG:A	donor_gain	0.8500

AlphaMissense

1652 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:6330474:G:C	F227L	0.855
7:6330474:G:T	F227L	0.855
7:6330476:A:G	F227L	0.855
7:6330813:A:C	F114L	0.806
7:6330813:A:T	F114L	0.806
7:6330815:A:G	F114L	0.806
7:6330519:G:C	F212L	0.799
7:6330519:G:T	F212L	0.799
7:6330521:A:G	F212L	0.799
7:6330495:A:C	F220L	0.787
7:6330495:A:T	F220L	0.787
7:6330497:A:G	F220L	0.787
7:6330405:A:C	F250L	0.729
7:6330405:A:T	F250L	0.729
7:6330407:A:G	F250L	0.729
7:6330471:C:A	K228N	0.656
7:6330471:C:G	K228N	0.656
7:6331149:C:A	R2S	0.634
7:6331149:C:G	R2S	0.634
7:6330960:C:A	M65I	0.631
7:6330960:C:G	M65I	0.631
7:6330960:C:T	M65I	0.631
7:6330630:A:C	F175L	0.624
7:6330630:A:T	F175L	0.624
7:6330632:A:G	F175L	0.624
7:6330654:A:C	F167L	0.614
7:6330654:A:T	F167L	0.614
7:6330656:A:G	F167L	0.614
7:6331017:C:A	W46C	0.583
7:6331017:C:G	W46C	0.583

dbSNP variants (sampled 300 via entrez): RS1000065705 (7:6339876 G>A,T), RS1000137293 (7:6348798 T>C), RS1000416847 (7:6340009 T>C), RS1000483518 (7:6332952 A>G), RS1000717823 (7:6347526 AAAAG>A), RS1000768632 (7:6331360 A>C,G), RS1000803810 (7:6346798 T>C), RS1000890663 (7:6343042 AAAAAAAG>A), RS1000947128 (7:6347960 G>C), RS1000948224 (7:6329240 G>A,T), RS1001064540 (7:6347824 T>C), RS1001212996 (7:6333425 G>C), RS1001321435 (7:6330557 G>A,C), RS1001515512 (7:6338493 G>C,T), RS1001560003 (7:6345116 CTTG>C)

Disease associations

OMIM: gene MIM:616628 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005951_155	Body mass index	1.000000e-08
GCST006998_2	Cerebrospinal fluid p-tau levels in mild cognitive impairment	9.000000e-08
GCST90002389_143	Lymphocyte percentage of white cells	8.000000e-15
GCST90002399_164	Neutrophil percentage of white cells	2.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004760	t-tau measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Zinc	decreases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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