MISFA

Summary

MISFA (mitochondrial sheath formation associated, HGNC:44122) is a protein-coding gene on chromosome 11p15.1, encoding Mitochondrial sheath formation-associated protein (A0A0U1RRN3). Regulates sperm development.

Predicted to be involved in sperm mitochondrial sheath assembly. Predicted to be located in mitochondrial outer membrane.

Source: NCBI Gene 100506540 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001355570

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44122
Approved symbol	MISFA
Name	mitochondrial sheath formation associated
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	Kastor, Polluks, TSCL1
Ensembl gene	ENSG00000247595
Ensembl biotype	protein_coding
OMIM	620764
Entrez	100506540

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000501599, ENST00000511927, ENST00000542172, ENST00000634992, ENST00000635674, ENST00000636011, ENST00000636313

RefSeq mRNA: 1 — MANE Select: NM_001355570 NM_001355570

CCDS: CCDS86186

Canonical transcript exons

ENST00000635674 — 4 exons

Exon	Start	End
ENSE00001979960	18601092	18601180
ENSE00001990229	18603158	18603195
ENSE00002232790	18599789	18599997
ENSE00003789542	18603772	18603883

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5216 / max 189.4557, expressed in 1470 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113350	3.3677	1470
113353	0.1094	5
113351	0.0412	4
113352	0.0033	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.70	gold quality
left testis	UBERON:0004533	99.26	gold quality
right testis	UBERON:0004534	99.10	gold quality
testis	UBERON:0000473	95.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.66	gold quality
adult organism	UBERON:0007023	89.00	gold quality
apex of heart	UBERON:0002098	85.23	gold quality
right atrium auricular region	UBERON:0006631	85.12	gold quality
gastrocnemius	UBERON:0001388	84.75	gold quality
cardiac atrium	UBERON:0002081	84.30	gold quality
pancreatic ductal cell	CL:0002079	84.24	silver quality
muscle of leg	UBERON:0001383	84.14	gold quality
heart left ventricle	UBERON:0002084	83.37	gold quality
cardiac ventricle	UBERON:0002082	82.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.11	gold quality
heart	UBERON:0000948	81.59	gold quality
adrenal tissue	UBERON:0018303	80.65	gold quality
left ventricle myocardium	UBERON:0006566	79.49	gold quality
epithelial cell of pancreas	CL:0000083	79.08	gold quality
right ovary	UBERON:0002118	78.56	gold quality
metanephros cortex	UBERON:0010533	77.96	gold quality
cardiac muscle of right atrium	UBERON:0003379	77.85	gold quality
skin of leg	UBERON:0001511	77.57	gold quality
left adrenal gland cortex	UBERON:0035825	77.42	gold quality
skin of abdomen	UBERON:0001416	77.19	gold quality
left adrenal gland	UBERON:0001234	76.87	gold quality
right uterine tube	UBERON:0001302	76.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.69	gold quality
adenohypophysis	UBERON:0002196	76.39	gold quality
right lobe of thyroid gland	UBERON:0001119	76.28	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	4476.18
E-ANND-3	no	2.33

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Identification of an interactome network between lncRNAs and miRNAs in thyroid cancer reveals SPTY2D1-AS1 as a new tumor suppressor. (PMID:35562181)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Mitochondrial sheath formation-associated protein — A0A0U1RRN3 (reviewed: A0A0U1RRN3)

Alternative names: Putative transmembrane protein SPTY2D1OS, SPTY2D1 antisense RNA 1, SPTY2D1 opposite strand

All UniProt accessions (3): A0A0U1RQQ8, A0A0U1RR47, A0A0U1RRN3

UniProt curated annotations — full annotation on UniProt →

Function. Regulates sperm development. May be involved in mitochondrial sheath formation. Regulates sperm development. May be involved in mitochondrial sheath formation.

Subunit / interactions. Interacts with VDAC3. Interacts with VDAC3.

Subcellular location. Mitochondrion outer membrane Mitochondrion outer membrane.

Miscellaneous. Isoform Kastor and isoform Polluks are conserved only in mammals.

Isoforms (2)

UniProt ID	Names	Canonical?
A0A0U1RRN3-1	Kastor	yes
A0A0U1RRN3-2	Polluks

RefSeq proteins (1): NP_001342499* (*=MANE)

Domains & families (InterPro)

UniProt features (7 total): transmembrane region 2, splice variant 2, topological domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A0U1RRN3-F1	68.60	0.08

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 26 (showing top): GOCC_MITOCHONDRIAL_ENVELOPE, GOCC_ORGANELLE_ENVELOPE, GLI4_TARGET_GENES, ID2_TARGET_GENES, ZNF407_TARGET_GENES, ZNF8_TARGET_GENES, GSE10273_HIGH_IL7_VS_HIGH_IL7_AND_IRF4_IN_IRF4_8_NULL_PRE_BCELL_DN, GSE13229_IMM_VS_INTMATURE_NKCELL_UP, GSE13229_MATURE_VS_INTMATURE_NKCELL_UP, GSE15733_BM_VS_SPLEEN_MEMORY_CD4_TCELL_UP, DESCARTES_MAIN_FETAL_ELF3_AGBL2_POSITIVE_CELLS, ZNF224_TARGET_GENES, HOEK_NK_CELL_2011_2012_TIV_3D_VS_0DY_ADULT_3D_DN, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_0.5H_ACT_CD4_TCELL_DN, GSE18148_CBFB_KO_VS_WT_TREG_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): mitochondrial outer membrane (GO:0005741), mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrial membrane	1
organelle outer membrane	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

70 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MISFA	C1orf185	Q5T7R7	445
MISFA	TNNC1	P02590	418
MISFA	Q3MI93	Q3MI93	398
MISFA	GARIN5A	Q6IPT2	397
MISFA	ADAM29	Q9UKF5	375
MISFA	TNP1	P09430	316
MISFA	NUP210L	Q5VU65	306
MISFA	Q8NG57	Q8NG57	288
MISFA	RFTN2	Q52LD8	284
MISFA	TPM2	P06468	277
MISFA	INSL3	P51460	276
MISFA	ADAT1	Q9BUB4	274
MISFA	ACTG2	P12718	261
MISFA	PKDREJ	Q9NTG1	250
MISFA	TPPP2	P59282	248

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0U1RRN3, A0T0A3, A0T0U2, A4IHD1, A5GIB0, B2JA13, B7K6Q5, C9JBD0, E9Q9R3, O64242, O70337, O70903, P04601, P0C420, P0C421, P0C422, P10302, P19052, P30637, P35091, P49473, P86994, Q05268, Q06FN9, Q06J11, Q0IDJ7, Q0VDE8, Q16517, Q3AN56, Q3J8F4, Q3KPU7, Q3M4N8, Q4G3C2, Q61979, Q6B8K4, Q6ENE5, Q6JL78, Q7U9P9, Q86Y28, Q8C5Y2

Diamond homologs: A0A0U1RRN3, Q8C5Y2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

666 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18601181:G:GG	donor_gain	0.9900
11:18603770:A:AG	acceptor_gain	0.9900
11:18603771:G:GG	acceptor_gain	0.9900
11:18609955:C:CC	acceptor_gain	0.9900
11:18599842:GTTTC:G	donor_gain	0.9800
11:18603767:CACA:C	acceptor_loss	0.9800
11:18603768:ACAG:A	acceptor_loss	0.9800
11:18603770:AGAC:A	acceptor_loss	0.9800
11:18609950:TTAAG:T	acceptor_gain	0.9800
11:18609951:TAAG:T	acceptor_gain	0.9800
11:18609955:CT:C	acceptor_loss	0.9800
11:18599847:G:GG	donor_gain	0.9700
11:18601178:GCA:G	donor_gain	0.9700
11:18603091:G:A	acceptor_gain	0.9700
11:18603193:GGG:G	donor_gain	0.9700
11:18603194:GG:G	donor_gain	0.9700
11:18603194:GGG:G	donor_gain	0.9700
11:18603195:GG:G	donor_gain	0.9700
11:18603196:G:GG	donor_gain	0.9700
11:18603771:GA:G	acceptor_gain	0.9700
11:18599846:C:CG	donor_gain	0.9600
11:18609953:AG:A	acceptor_gain	0.9600
11:18601084:T:A	acceptor_gain	0.9500
11:18603090:T:TA	acceptor_gain	0.9400
11:18603196:G:A	donor_loss	0.9400
11:18603197:T:A	donor_loss	0.9400
11:18603771:GACT:G	acceptor_gain	0.9400
11:18609865:CGCCT:C	donor_gain	0.9400
11:18603769:C:G	acceptor_gain	0.9300
11:18609952:AAG:A	acceptor_gain	0.9200

AlphaMissense

384 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:18599944:T:A	W6R	0.939
11:18599944:T:C	W6R	0.939
11:18599983:T:C	F19L	0.848
11:18599985:T:A	F19L	0.848
11:18599985:T:G	F19L	0.848
11:18599959:G:A	G11R	0.846
11:18599959:G:C	G11R	0.846
11:18599957:T:A	V10D	0.822
11:18599948:T:G	M7R	0.819
11:18599941:G:C	G5R	0.817
11:18599948:T:A	M7K	0.781
11:18599960:G:A	G11E	0.778
11:18599939:T:A	L4H	0.720
11:18599953:T:C	F9L	0.715
11:18599955:T:A	F9L	0.715
11:18599955:T:G	F9L	0.715
11:18599946:G:C	W6C	0.661
11:18599946:G:T	W6C	0.661
11:18599968:T:C	C14R	0.660
11:18599936:T:A	V3E	0.642
11:18599942:G:A	G5D	0.640
11:18601109:G:C	W29C	0.622
11:18601109:G:T	W29C	0.622
11:18599977:G:C	G17R	0.609
11:18599939:T:G	L4R	0.594
11:18599977:G:T	G17C	0.594
11:18599933:T:A	I2N	0.586
11:18599971:T:G	Y15D	0.582
11:18599963:T:A	L12H	0.579
11:18599966:T:A	V13E	0.578

dbSNP variants (sampled 300 via entrez): RS1000018382 (11:18599636 G>A,T), RS1000525334 (11:18605403 C>A), RS1000583146 (11:18599753 C>T), RS1000913555 (11:18604401 A>T), RS1000959804 (11:18605698 T>C), RS1000965535 (11:18604648 C>T), RS1001126461 (11:18598279 G>A), RS1001364059 (11:18601255 T>G), RS1001476154 (11:18597816 C>A,T), RS1001583079 (11:18600977 G>A,T), RS1002208321 (11:18605254 AAAGAG>A), RS1002309401 (11:18598818 T>A,C), RS1002356964 (11:18602628 A>G), RS1002544323 (11:18605010 A>G), RS1002659587 (11:18602346 G>A)

Disease associations

OMIM: gene MIM:620764 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
methylmercuric chloride	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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