Mutagenetix > Incidental Mutation

Incidental Mutation 'R1754:Fgfr1'

193844

Institutional Source

Beutler Lab

Gene Symbol

Fgfr1

Ensembl Gene

ENSMUSG00000031565

Gene Name

fibroblast growth factor receptor 1

Synonyms

Eask, Hspy, Fgfr-1, Flt-2

MMRRC Submission

039786-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1754 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

25513654-25575718 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 25570210 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Arginine at position 552 (H552R)

Ref Sequence

ENSEMBL: ENSMUSP00000136640 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000084027] [ENSMUST00000117179] [ENSMUST00000119398] [ENSMUST00000167764] [ENSMUST00000178276] [ENSMUST00000179592]

AlphaFold

P16092

Predicted Effect

probably damaging
Transcript: ENSMUST00000084027
AA Change: H541R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000081041
Gene: ENSMUSG00000031565
AA Change: H541R

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
IGc2	46	108	2.94e-10	SMART
low complexity region	124	138	N/A	INTRINSIC
IGc2	169	237	4.09e-9	SMART
IGc2	268	348	1.26e-9	SMART
transmembrane domain	375	397	N/A	INTRINSIC
low complexity region	439	453	N/A	INTRINSIC
TyrKc	478	754	1.51e-155	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000117179
AA Change: H539R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000113909
Gene: ENSMUSG00000031565
AA Change: H539R

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
IGc2	46	108	2.94e-10	SMART
low complexity region	124	138	N/A	INTRINSIC
IGc2	167	235	4.09e-9	SMART
IGc2	266	346	1.26e-9	SMART
transmembrane domain	373	395	N/A	INTRINSIC
low complexity region	437	451	N/A	INTRINSIC
TyrKc	476	752	1.51e-155	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000119398
AA Change: H452R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000113855
Gene: ENSMUSG00000031565
AA Change: H452R

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
low complexity region	35	49	N/A	INTRINSIC
IGc2	80	148	4.09e-9	SMART
IGc2	179	259	1.26e-9	SMART
transmembrane domain	286	308	N/A	INTRINSIC
low complexity region	350	364	N/A	INTRINSIC
TyrKc	389	665	1.51e-155	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000120106

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000126118

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133936

Predicted Effect

probably benign
Transcript: ENSMUST00000138104

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145218

Predicted Effect

probably damaging
Transcript: ENSMUST00000167764
AA Change: H452R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000131343
Gene: ENSMUSG00000031565
AA Change: H452R

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
low complexity region	35	49	N/A	INTRINSIC
IGc2	78	146	4.09e-9	SMART
IGc2	177	255	1.22e-7	SMART
transmembrane domain	286	308	N/A	INTRINSIC
low complexity region	350	364	N/A	INTRINSIC
TyrKc	389	665	1.51e-155	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000178276
AA Change: H452R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000137515
Gene: ENSMUSG00000031565
AA Change: H452R

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
low complexity region	35	49	N/A	INTRINSIC
IGc2	78	146	4.09e-9	SMART
IGc2	177	255	1.22e-7	SMART
transmembrane domain	286	308	N/A	INTRINSIC
low complexity region	350	364	N/A	INTRINSIC
TyrKc	389	665	1.51e-155	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000179592
AA Change: H552R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000136640
Gene: ENSMUSG00000031565
AA Change: H552R

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
IGc2	59	121	2.94e-10	SMART
low complexity region	137	151	N/A	INTRINSIC
IGc2	180	248	4.09e-9	SMART
IGc2	279	359	1.26e-9	SMART
transmembrane domain	386	408	N/A	INTRINSIC
low complexity region	450	464	N/A	INTRINSIC
TyrKc	489	765	1.51e-155	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211419

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000210504

Coding Region Coverage

1x: 97.5%
3x: 97.0%
10x: 95.6%
20x: 93.3%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for targeted null mutations die around gastrulation and show defective patterning of axial structures. Hypomorphic and selectively ablated mutations exhibit a wide range of abnormalities affecting diverse structures. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930563D23Rik	A	G	16: 92,321,031	V123A	probably damaging	Het
Abca2	T	A	2: 25,434,333	L234M	probably benign	Het
Abca3	G	A	17: 24,377,779	S402N	probably benign	Het
Acad12	A	T	5: 121,607,481	V249D	probably benign	Het
Acp4	T	C	7: 44,255,004	I212V	probably benign	Het
Actl6a	T	A	3: 32,718,574	V233D	probably damaging	Het
Aire	T	A	10: 78,030,290	Q533L	probably damaging	Het
Aldh3b3	T	C	19: 3,968,517	S411P	probably benign	Het
Amer2	A	G	14: 60,379,757	K467R	probably damaging	Het
Apol9b	A	T	15: 77,735,762	I253F	probably benign	Het
Arid1b	A	G	17: 5,279,201		probably null	Het
Atp6v0a4	T	C	6: 38,067,829	T494A	probably benign	Het
Atp6v1b2	A	G	8: 69,101,961	D106G	probably benign	Het
Avpr1b	T	C	1: 131,600,101	S121P	probably damaging	Het
Bcl11a	A	C	11: 24,164,724	E689A	probably damaging	Het
Brpf3	T	G	17: 28,821,323	L906R	probably benign	Het
Btn1a1	T	C	13: 23,460,468	K287E	probably benign	Het
Cacna1i	A	G	15: 80,371,529	H871R	probably damaging	Het
Cd14	A	T	18: 36,725,514	L296Q	probably damaging	Het
Col1a2	G	A	6: 4,518,822		probably benign	Het
Colgalt1	G	T	8: 71,623,179	W490L	probably damaging	Het
Ctnna2	A	G	6: 77,636,749	I273T	possibly damaging	Het
Dnah7a	A	C	1: 53,561,900		probably null	Het
Dnah7a	A	T	1: 53,504,185	D2275E	probably benign	Het
Egfem1	T	C	3: 29,668,333	Y404H	possibly damaging	Het
Esm1	A	T	13: 113,216,696	N171Y	probably damaging	Het
Exoc1	T	G	5: 76,560,322		probably null	Het
Fcho1	A	G	8: 71,711,246	I580T	probably benign	Het
Fsbp	A	G	4: 11,583,906	R202G	probably damaging	Het
Gabra6	A	G	11: 42,316,561	V231A	probably damaging	Het
Gm8765	A	T	13: 50,701,087	T254S	probably damaging	Het
Gmeb1	A	G	4: 132,232,027	S239P	probably benign	Het
Gnpat	T	A	8: 124,877,006	Y208N	probably damaging	Het
Il21	T	C	3: 37,225,525	K114R	possibly damaging	Het
Inhbc	T	C	10: 127,370,293	D35G	possibly damaging	Het
Inpp4b	A	T	8: 81,770,811	T87S	probably damaging	Het
Kcns2	T	C	15: 34,839,517	I342T	possibly damaging	Het
Ky	A	T	9: 102,541,927	T378S	possibly damaging	Het
Lcat	CAT	C	8: 105,941,814		probably null	Het
Lrrc8d	T	C	5: 105,812,657	V311A	probably benign	Het
Mief1	A	G	15: 80,249,602	I287V	probably damaging	Het
Mrpl47	A	G	3: 32,730,084	V179A	probably benign	Het
Mtcl1	T	C	17: 66,380,183	K576R	probably damaging	Het
Myh10	C	A	11: 68,813,058	A1902E	probably damaging	Het
Nlrp3	A	G	11: 59,558,402	T837A	possibly damaging	Het
Nr1i3	T	C	1: 171,217,394	Y132H	probably damaging	Het
Oit3	T	C	10: 59,427,940		probably null	Het
Olfr1186	A	T	2: 88,525,815	R77S	probably damaging	Het
Olfr1467	T	C	19: 13,365,353	S242P	probably damaging	Het
Olfr193	T	A	16: 59,110,581	I10F	probably benign	Het
Olfr30	A	T	11: 58,455,262	M229K	probably damaging	Het
Olfr427	A	G	1: 174,100,033	T192A	probably benign	Het
Olfr533	A	T	7: 140,466,860	I220F	probably damaging	Het
Olfr8	T	A	10: 78,955,697	V164E	probably damaging	Het
Olfr825	G	A	10: 130,163,164	T54I	probably benign	Het
Pdlim4	T	C	11: 54,055,873	E196G	possibly damaging	Het
Pigs	A	G	11: 78,337,847	Y293C	probably damaging	Het
Pkd1l2	A	T	8: 117,030,719	S1527T	possibly damaging	Het
Pkd2l1	A	T	19: 44,155,601	Y344*	probably null	Het
Pmp2	T	C	3: 10,182,224		probably null	Het
Polr3e	T	C	7: 120,939,298		probably null	Het
Ppp3ca	C	G	3: 136,881,448	I230M	probably benign	Het
Ppp5c	T	C	7: 17,005,310	H463R	probably benign	Het
Ptger1	A	G	8: 83,669,297	N328D	probably benign	Het
Rhno1	A	T	6: 128,357,859	I167N	probably benign	Het
Rictor	C	A	15: 6,735,368	P34H	probably damaging	Het
Rnf10	A	C	5: 115,245,865	S630R	probably damaging	Het
Rnf168	A	G	16: 32,299,124	Q501R	probably benign	Het
Rngtt	T	G	4: 33,329,634		probably null	Het
Samd9l	G	T	6: 3,373,126	F1378L	probably damaging	Het
Slc9c1	T	A	16: 45,589,509	M864K	probably benign	Het
Slitrk5	T	C	14: 111,680,519	F525S	probably damaging	Het
Sox6	T	C	7: 115,477,055	M784V	probably benign	Het
Spint2	C	T	7: 29,260,366		probably null	Het
Ssh1	A	T	5: 113,955,845	I276N	probably damaging	Het
Trank1	T	A	9: 111,392,871	V2892D	probably benign	Het
Ttn	C	A	2: 76,751,040	E21424*	probably null	Het
Usp17lc	T	C	7: 103,418,848	I450T	probably benign	Het
Vcan	A	G	13: 89,704,735	V702A	probably benign	Het
Vmn1r36	TA	TAA	6: 66,716,533		probably null	Het
Vmn2r51	G	T	7: 10,099,946	D388E	probably benign	Het
Zfp106	G	A	2: 120,533,763	S721L	probably damaging	Het
Zfp106	A	C	2: 120,533,764	S721A	probably damaging	Het
Zfp189	T	A	4: 49,529,342	H148Q	possibly damaging	Het
Zfp352	A	T	4: 90,223,809	Y62F	probably benign	Het
Zfp839	T	C	12: 110,855,457	V235A	probably damaging	Het
Zfp871	T	C	17: 32,775,334	Y289C	probably damaging	Het

Other mutations in Fgfr1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01413:Fgfr1	APN	8	25562223	nonsense	probably null
IGL01537:Fgfr1	APN	8	25555579	missense	probably damaging	1.00
IGL01643:Fgfr1	APN	8	25566735	missense	probably benign	0.01
IGL01875:Fgfr1	APN	8	25573553	missense	possibly damaging	0.81
IGL02002:Fgfr1	APN	8	25555711	missense	probably damaging	1.00
IGL02698:Fgfr1	APN	8	25573608	nonsense	probably null
IGL02822:Fgfr1	APN	8	25557802	missense	probably benign	0.13
IGL03292:Fgfr1	APN	8	25557755	missense	possibly damaging	0.50
R0003:Fgfr1	UTSW	8	25568198	missense	possibly damaging	0.80
R0723:Fgfr1	UTSW	8	25557768	missense	probably damaging	0.99
R0730:Fgfr1	UTSW	8	25555744	missense	probably benign
R1144:Fgfr1	UTSW	8	25558143	missense	probably damaging	1.00
R1455:Fgfr1	UTSW	8	25562276	missense	possibly damaging	0.81
R1591:Fgfr1	UTSW	8	25572720	missense	probably damaging	1.00
R2045:Fgfr1	UTSW	8	25558215	missense	probably benign	0.04
R2139:Fgfr1	UTSW	8	25570866	missense	probably damaging	1.00
R2314:Fgfr1	UTSW	8	25570893	missense	probably damaging	1.00
R2517:Fgfr1	UTSW	8	25563446	missense	probably damaging	1.00
R2982:Fgfr1	UTSW	8	25558211	missense	probably benign	0.04
R3796:Fgfr1	UTSW	8	25572437	missense	probably damaging	1.00
R3797:Fgfr1	UTSW	8	25572437	missense	probably damaging	1.00
R3799:Fgfr1	UTSW	8	25572437	missense	probably damaging	1.00
R4323:Fgfr1	UTSW	8	25573899	missense	probably benign	0.37
R4594:Fgfr1	UTSW	8	25573836	missense	probably damaging	0.99
R4614:Fgfr1	UTSW	8	25557797	missense	probably benign	0.25
R4696:Fgfr1	UTSW	8	25563488	missense	probably damaging	0.99
R4916:Fgfr1	UTSW	8	25563526	critical splice donor site	probably null
R4966:Fgfr1	UTSW	8	25572445	nonsense	probably null
R5094:Fgfr1	UTSW	8	25570165	missense	probably damaging	1.00
R5730:Fgfr1	UTSW	8	25573811	missense	probably damaging	1.00
R5911:Fgfr1	UTSW	8	25519309	utr 5 prime	probably benign
R7310:Fgfr1	UTSW	8	25562315	missense	probably benign	0.01
R7326:Fgfr1	UTSW	8	25573839	missense	probably damaging	1.00
R7404:Fgfr1	UTSW	8	25555550	missense	probably benign
R7611:Fgfr1	UTSW	8	25558205	nonsense	probably null
R7681:Fgfr1	UTSW	8	25555661	missense	probably damaging	0.98
R7738:Fgfr1	UTSW	8	25558185	missense	probably damaging	0.96
R7789:Fgfr1	UTSW	8	25562313	nonsense	probably null
R7958:Fgfr1	UTSW	8	25532342	missense	probably benign
R8206:Fgfr1	UTSW	8	25570242	missense	probably damaging	1.00
R8236:Fgfr1	UTSW	8	25562272	nonsense	probably null
R8691:Fgfr1	UTSW	8	25562237	missense	possibly damaging	0.95
R9124:Fgfr1	UTSW	8	25570169	missense	probably damaging	1.00
R9633:Fgfr1	UTSW	8	25570760	missense	probably damaging	1.00
R9704:Fgfr1	UTSW	8	25573563	missense	probably benign	0.01
R9798:Fgfr1	UTSW	8	25563507	missense	unknown
Z1177:Fgfr1	UTSW	8	25563398	missense	probably benign	0.00
Z1177:Fgfr1	UTSW	8	25570768	missense	possibly damaging	0.67

Predicted Primers

PCR Primer
(F):5'- AGTCACGGCTCACACTGTCACTAC -3'
(R):5'- AAGTTCCCAAGCGAAGCTGAGG -3'

Sequencing Primer
(F):5'- ACTACATGGTAGTAGTGGCTCC -3'
(R):5'- GTAGGTGCCCTAATGTAGACTC -3'

Posted On

2014-05-23