RAD21L1

Summary

RAD21L1 (RAD21 cohesin complex component like 1, HGNC:16271) is a protein-coding gene on chromosome 20p13, encoding Double-strand-break repair protein rad21-like protein 1 (Q9H4I0). Meiosis-specific component of some cohesin complex required during the initial steps of prophase I in male meiosis.

Predicted to enable chromatin binding activity. Predicted to be involved in replication-born double-strand break repair via sister chromatid exchange and sister chromatid cohesion. Predicted to act upstream of or within several processes, including double-strand break repair via homologous recombination; homologous chromosome segregation; and seminiferous tubule development. Predicted to be located in chromosome and nucleus. Predicted to be part of meiotic cohesin complex.

Source: NCBI Gene 642636 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 69 total — 1 pathogenic
• MANE Select transcript: NM_001384355

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16271
Approved symbol	RAD21L1
Name	RAD21 cohesin complex component like 1
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	dJ545L17.2, RAD21L
Ensembl gene	ENSG00000244588
Ensembl biotype	protein_coding
OMIM	619533
Entrez	642636

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000246108, ENST00000402452, ENST00000409241, ENST00000477283, ENST00000683101, ENST00000947764

RefSeq mRNA: 5 — MANE Select: NM_001384355 NM_001136566, NM_001384355, NM_001384356, NM_001384357, NM_001384358

CCDS: CCDS46568, CCDS92998

Canonical transcript exons

ENST00000683101 — 14 exons

Exon	Start	End
ENSE00000858578	1228422	1228597
ENSE00000858579	1229880	1230009
ENSE00000990885	1242619	1242845
ENSE00000990886	1243097	1243196
ENSE00000990887	1244046	1244170
ENSE00000990889	1248626	1248703
ENSE00001490138	1239312	1239407
ENSE00001551138	1234085	1234191
ENSE00001557704	1240321	1240434
ENSE00001558193	1238044	1238214
ENSE00003623317	1231526	1231619
ENSE00003918597	1226044	1226140
ENSE00003920095	1246213	1246305
ENSE00003921290	1254269	1255876

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 88.69.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1356 / max 13.5325, expressed in 65 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183090	0.1272	65
208967	0.0084	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	88.69	gold quality
male germ cell	CL:0000015	85.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.14	gold quality
buccal mucosa cell	CL:0002336	79.27	silver quality
right testis	UBERON:0004534	75.67	gold quality
left testis	UBERON:0004533	74.06	gold quality
testis	UBERON:0000473	72.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.61	gold quality
lower lobe of lung	UBERON:0008949	58.00	silver quality
myocardium	UBERON:0002349	51.72	gold quality
right lung	UBERON:0002167	51.56	gold quality
left ventricle myocardium	UBERON:0006566	51.17	gold quality
cardiac muscle of right atrium	UBERON:0003379	51.07	gold quality
upper arm skin	UBERON:0004263	50.47	gold quality
epithelial cell of pancreas	CL:0000083	50.29	gold quality
quadriceps femoris	UBERON:0001377	50.29	gold quality
nasal cavity epithelium	UBERON:0005384	50.01	gold quality
deltoid	UBERON:0001476	49.93	gold quality
vastus lateralis	UBERON:0001379	49.69	gold quality
tendon of biceps brachii	UBERON:0008188	49.32	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
tibialis anterior	UBERON:0001385	48.95	silver quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.90

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• RAD21L is identified as a novel cohesin complex subunit homologous to mammalian RAD21/REC8/alpha-kleisin subfamily. (PMID:21527826)
• The association of three single-nucleotide polymorphisms with azoospermia, especially Sertoli cell-only syndrome, was studied in Japanese men. (PMID:28635411)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rad21l	ENSMUSG00000074704
rattus_norvegicus	Rad21l1	ENSRNOG00000022335
drosophila_melanogaster	vtd	FBGN0260987

Paralogs (2): REC8 (ENSG00000100918), RAD21 (ENSG00000164754)

Protein

Protein identifiers

Double-strand-break repair protein rad21-like protein 1 — Q9H4I0 (reviewed: Q9H4I0)

All UniProt accessions (3): Q9H4I0, A0A140T8W2, A0A804HJ87

UniProt curated annotations — full annotation on UniProt →

Function. Meiosis-specific component of some cohesin complex required during the initial steps of prophase I in male meiosis. Probably required during early meiosis in males for separation of sister chromatids and homologous chromosomes. Replaces RAD21 in premeiotic S phase (during early stages of prophase I), while RAD21 reappears in later stages of prophase I. Involved in synaptonemal complex assembly, synapsis initiation and crossover recombination between homologous chromosomes during prophase I.

Subunit / interactions. Component of some meiotic cohesin complex composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their hinge domain, RAD21L which link them, and STAG3.

Subcellular location. Nucleus. Chromosome.

Similarity. Belongs to the rad21 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H4I0-1	1	yes
Q9H4I0-2	2

RefSeq proteins (5): NP_001130038, NP_001371284, NP_001371285, NP_001371286, NP_001371287 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006909	Rad21/Rec8_C_eu	Domain
IPR006910	Rad21_Rec8_N	Domain
IPR023093	ScpA-like_C	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR039781	Rad21/Rec8-like	Family
IPR049589	NXP1_M-like	Domain

Pfam: PF04824, PF04825

UniProt features (8 total): sequence variant 4, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4I0-F1	61.56	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 29 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_SISTER_CHROMATID_COHESION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_RECOMBINATIONAL_REPAIR, GOBP_MEIOTIC_CELL_CYCLE, GOMF_CHROMATIN_BINDING, GOCC_COHESIN_COMPLEX, GOBP_CELL_CYCLE_PROCESS, GOBP_DNA_METABOLIC_PROCESS, GOBP_DNA_REPAIR, GOBP_DNA_RECOMBINATION, GOBP_CHROMOSOME_SEGREGATION, GOBP_ESTABLISHMENT_OF_SISTER_CHROMATID_COHESION, GOCC_MEIOTIC_COHESIN_COMPLEX, GOBP_REPLICATION_BORN_DOUBLE_STRAND_BREAK_REPAIR_VIA_SISTER_CHROMATID_EXCHANGE

GO Biological Process (12): chromosome segregation (GO:0007059), sister chromatid cohesion (GO:0007062), meiotic cell cycle (GO:0051321), replication-born double-strand break repair via sister chromatid exchange (GO:1990414), double-strand break repair via homologous recombination (GO:0000724), double-strand break repair (GO:0006302), homologous chromosome pairing at meiosis (GO:0007129), synaptonemal complex assembly (GO:0007130), spermatogenesis (GO:0007283), fertilization (GO:0009566), meiotic attachment of telomere to nuclear envelope (GO:0070197), seminiferous tubule development (GO:0072520)

GO Molecular Function (2): chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), chromosome (GO:0005694), meiotic cohesin complex (GO:0030893), condensed nuclear chromosome (GO:0000794), lateral element (GO:0000800), cohesin complex (GO:0008278)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell cycle process	2
sexual reproduction	2
reproductive process	2
chromosome organization involved in meiotic cell cycle	2
binding	2
chromosome organization	1
cell cycle	1
meiotic nuclear division	1
double-strand break repair via homologous recombination	1
recombinational repair	1
double-strand break repair	1
DNA repair	1
homologous chromosome segregation	1
homologous chromosome pairing at meiosis	1
cellular component assembly	1
synaptonemal complex organization	1
developmental process involved in reproduction	1
male gamete generation	1
meiotic telomere tethering at nuclear periphery	1
chromosome attachment to the nuclear envelope	1
meiotic cell cycle process	1
male gonad development	1
tube development	1
reproductive structure development	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cohesin complex	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
synaptonemal complex	1
cellular anatomical structure	1
chromosome	1
protein-containing complex	1

Protein interactions and networks

STRING

1831 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD21L1	STAG3	Q9UJ98	997
RAD21L1	SMC1B	Q8NDV3	995
RAD21L1	SMC3	Q9UQE7	974
RAD21L1	REC8	O95072	941
RAD21L1	SMC1A	Q14683	937
RAD21L1	STAG2	Q8N3U4	803
RAD21L1	SPO11	Q9Y5K1	781
RAD21L1	SYCP1	Q15431	732
RAD21L1	SYCP3	Q8IZU3	721
RAD21L1	WAPL	Q7Z5K2	694
RAD21L1	HORMAD1	Q86X24	689
RAD21L1	STAG1	Q8WVM7	689
RAD21L1	ESPL1	Q14674	670
RAD21L1	SYCE1	Q8N0S2	644
RAD21L1	SYCE2	Q6PIF2	616

IntAct

0 interactions, top by confidence:

BioGRID (2): RAD21L1 (Biochemical Activity), RAD21L1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1P8AW69, A2AU37, A5LFW4, A6QPC8, B2ZX90, D2HSB3, F4HY56, F4I1T7, F4JET1, F4K3G5, O04539, O13067, O48686, P36626, Q0P4S5, Q0WPK4, Q15003, Q19325, Q28GV1, Q564K3, Q5RH01, Q641G4, Q66IH2, Q67W65, Q6A331, Q6A332, Q6A333, Q6AUQ7, Q8C156, Q8GSA7, Q8W1Y0, Q9C689, Q9C7C4, Q9FFH1, Q9FKV5, Q9FLL1, Q9FQ19, Q9FQ20, Q9FT92, Q9H4I0

Diamond homologs: A2AU37, D2HSB3, O60216, O93310, P30776, Q12158, Q3SWX9, Q61550, Q6TEL1, Q8W1Y0, Q9FQ19, Q9FQ20, Q9H4I0, Q9S7T7, O95072, Q19325, P36626, Q6AYJ4, Q8C5S7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RAD21L1	“form complex”	“RAD21L Cohesin complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	62
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1244230	NM_001384355.1(RAD21L1):c.85A>T (p.Lys29Ter)	Pathogenic

SpliceAI

3047 predictions. Top by Δscore:

Variant	Effect	Δscore
20:1228420:A:AG	acceptor_gain	1.0000
20:1228420:AGTTT:A	acceptor_gain	1.0000
20:1228421:G:GG	acceptor_gain	1.0000
20:1228421:GTT:G	acceptor_gain	1.0000
20:1228421:GTTT:G	acceptor_gain	1.0000
20:1228421:GTTTG:G	acceptor_gain	1.0000
20:1231520:TTTCA:T	acceptor_loss	1.0000
20:1231521:TTCAG:T	acceptor_loss	1.0000
20:1231522:TCAG:T	acceptor_loss	1.0000
20:1231523:CAGG:C	acceptor_loss	1.0000
20:1231524:A:AG	acceptor_gain	1.0000
20:1231524:A:G	acceptor_loss	1.0000
20:1231525:G:GG	acceptor_gain	1.0000
20:1231617:G:GT	donor_gain	1.0000
20:1231617:GAA:G	donor_gain	1.0000
20:1231620:G:GG	donor_gain	1.0000
20:1234083:A:AG	acceptor_gain	1.0000
20:1234084:G:GG	acceptor_gain	1.0000
20:1234084:GT:G	acceptor_gain	1.0000
20:1234084:GTGCT:G	acceptor_gain	1.0000
20:1239309:A:AG	acceptor_gain	1.0000
20:1239310:A:G	acceptor_gain	1.0000
20:1244035:T:A	acceptor_gain	1.0000
20:1244039:A:AG	acceptor_gain	1.0000
20:1244040:A:G	acceptor_gain	1.0000
20:1244044:A:AG	acceptor_gain	1.0000
20:1244045:G:GG	acceptor_gain	1.0000
20:1244167:TGAGG:T	donor_loss	1.0000
20:1244171:G:GA	donor_loss	1.0000
20:1244172:T:G	donor_loss	1.0000

AlphaMissense

3726 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:1228505:T:A	W18R	0.998
20:1228505:T:C	W18R	0.998
20:1229911:T:C	L59P	0.998
20:1228515:C:A	A21D	0.997
20:1228517:C:G	H22D	0.997
20:1229919:G:A	G62R	0.997
20:1229919:G:C	G62R	0.997
20:1229929:G:C	R65P	0.997
20:1229956:T:C	L74P	0.997
20:1228514:G:C	A21P	0.995
20:1229914:T:C	L60P	0.995
20:1228457:T:C	F2L	0.994
20:1228459:C:A	F2L	0.994
20:1228459:C:G	F2L	0.994
20:1228507:G:C	W18C	0.994
20:1228507:G:T	W18C	0.994
20:1229905:G:A	G57E	0.994
20:1228509:T:C	L19P	0.993
20:1229901:T:C	S56P	0.993
20:1229920:G:A	G62E	0.993
20:1228503:T:A	I17K	0.992
20:1228519:C:A	H22Q	0.992
20:1228519:C:G	H22Q	0.992
20:1228497:C:A	A15D	0.990
20:1228511:G:C	A20P	0.990
20:1228512:C:A	A20E	0.990
20:1229896:G:C	R54P	0.990
20:1229920:G:T	G62V	0.990
20:1229926:T:A	V64D	0.990
20:1229946:G:C	A71P	0.990

dbSNP variants (sampled 300 via entrez): RS1000143266 (20:1242572 T>C), RS1000155681 (20:1235329 A>C,G), RS1000168816 (20:1256359 A>G), RS1000209229 (20:1240764 A>G), RS1000272162 (20:1235472 A>T), RS1000380676 (20:1228231 A>T), RS1000429798 (20:1242231 G>T), RS1000484167 (20:1236735 A>C,G), RS1000597973 (20:1237046 G>A), RS1000632600 (20:1230722 ATCT>A), RS1000670418 (20:1227906 T>C), RS1000800350 (20:1250054 G>A,C), RS1000906362 (20:1224570 G>A,T), RS1000915277 (20:1230489 C>T), RS1001220102 (20:1224461 C>T)

Disease associations

OMIM: gene MIM:619533 | 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

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

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
2-palmitoylglycerol	increases expression	1
Benzo(a)pyrene	affects methylation	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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